Dmitri Kireev- Ph.D.
- Professor at University of Missouri
Dmitri Kireev
- Ph.D.
- Professor at University of Missouri
About
134
Publications
69,476
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Introduction
My broad expertise is in drug discovery and life sciences with a specific focus on computer-aided drug design. During over 20 years in the industry and academia, I have been involved in the discovery of several drugs and drug candidates, co-invented a kinase-targeted cancer therapeutic, currently in clinical trials, and co-authored over 80 patents and publications. My research program also includes computational biophysics and development of new CADD approaches.
Current institution
Additional affiliations
September 2008 - present
February 1997 - September 2008
June 1991 - August 1993
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Position
- Research Associate
Publications
Publications (134)
Understanding chromatin dynamics across multiple spatiotemporal scales requires models that reconcile biological specificity with physics-based interactions and computational tractability. We present a modular, recognition-enabled ultra-coarse-grained (UCG) framework that captures both histone-DNA and histone-histone interactions using site-specifi...
A critical assessment of computational hit-finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised of computational chemists and data scientists used protein structure and data from fragment-screening pai...
A critical assessment of computational hit finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised of computational chemists and data scientists used protein structure and data from fragment-screening pai...
A critical assessment of computational hit finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised of computational chemists and data scientists used protein structure and data from fragment-screening pai...
A critical assessment of computational hit finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised of computational chemists and data scientists used protein structure and data from fragment-screening pai...
Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the...
The CACHE challenges are a series of prospective benchmarking exercises meant to evaluate progress in the field of computational hit-finding. Here we report the results of the inaugural CACHE #1 challenge in which 23 computational teams each selected up to 100 commercially available compounds that they predicted would bind to the WDR domain of the...
Chemical probes are an indispensable tool for translating biological discoveries into new therapies, though are increasingly difficult to identify since novel therapeutic targets are often hard-to-drug proteins. We introduce FRASE-based hit-finding robot (FRASE-bot), to expedite drug discovery for unconventional therapeutic targets. FRASE-bot mines...
Background
Spleen associated tyrosine kinase (SYK) plays a potential role in several neurodegenerative conditions. To date, a few pharmacological inhibitors have been developed, targeting the ATP‐binding kinase domain, and some of these inhibitors have been reported to show beneficial effects on the pathophysiology of Alzheimer’s (PMC: 9179326 ).In...
Chemical probes are an indispensable tool for translating biological discoveries into new therapies, though are increasingly difficult to identify. Novel therapeutic targets are often hard-to-drug proteins, such as messengers or transcription factors. Computational strategies arise as a promising solution to expedite drug discovery for unconvention...
Background
Spleen tyrosine kinase (SYK) and FCεR1γ were identified as targets for Alzheimer’s disease (AD) via multi‐omics human data by AMP‐AD teams. These proteins were selected for further target validation and medicinal chemistry efforts by members of the Target Enablement to Accelerate Therapy Development for Alzheimer’s Disease (TREAT‐AD) pro...
Gene regulation plays essential roles in all multicellular organisms allowing for different specialized tissue types to be generated from a complex genome. Heterochromatin-driven gene repression, associated with a physical compaction of the genome, is a pathway involving core components that are conserved from yeast to human. Posttranslational modi...
Bivalent chemical degraders, otherwise known as proteolysis-targeting chimeras (PROTACs), have proven to be an efficient strategy for targeting overexpressed or mutated proteins in cancer. PROTACs provide an alternative approach to small-molecule inhibitors, which are restricted by occupancy-driven pharmacology, often resulting in acquired inhibito...
The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic patch recognition proteome wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K...
mRNA display is a powerful, high-throughput technology for discovering novel, peptide ligands for protein targets. A number of methods have been used to expand the chemical diversity of mRNA display libraries beyond the 20 canonical amino acids, including genetic code reprogramming and biorthogonal chemistries. To date, however, there have been few...
DNA-encoded chemical libraries (DECLs) interrogate the interactions of a target of interest with vast numbers of molecules. DECLs hence provide abundant information about the chemical ligand space for therapeutic targets, and there is considerable interest in methods for exploiting DECL screening data to predict novel ligands. Here we introduce one...
Mutations in the small GTPase protein KRAS are one of the leading drivers of cancers including lung, pancreatic, and colorectal, as well as a group of developmental disorders termed “Rasopathies”. Recent breakthroughs in the development of mutant-specific KRAS inhibitors include the FDA approved drug Lumakras (Sotorasib, AMG510) for KRAS G12C-mutat...
Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI), and the mechanisms are not well defined. The MERTK ligand GAS6 promoted downstream oncogenic signaling in EGFR-mutated (EGFRMT) NSCLC cells treated with OSI, suggesting a role for MERTK activation in OSI resistance. Indeed, treatment with MRX-2...
Heterochromatin is a physical state of the chromatin fiber that maintains gene repression during cell development. Although evidence exists on molecular mechanisms involved in heterochromatin formation, a detailed structural mechanism of heterochromatin formation needs a better understanding. We made use of a simple Monte-Carlo simulation model wit...
Introduction:
The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP AD) program.
Methods:
Publicly available resources, such as literature and databases, enabled a data-driven effort to identify existing small molecule modulators for many...
Introduction:
A chemogenomic set of small molecules with annotated activities and implicated roles in Alzheimer's disease (AD) called the AD Informer Set was recently developed and made available to the AD research community: https://treatad.org/data-tools/ad-informer-set/.
Methods:
Small subsets of AD Informer Set compounds were selected for AD...
A key role of chromatin kinases is to phosphorylate histone tails during mitosis to spatiotemporally regulate cell division. Vaccinia-related kinase 1 (VRK1) is a serine–threonine kinase that phosphorylates histone H3 threonine 3 (H3T3) along with other chromatin-based targets. While structural studies have defined how several classes of histone-mo...
Nuclear receptor-binding SET domain-containing 2 (NSD2) is the primary enzyme responsible for the dimethylation of lysine 36 of histone 3 (H3K36), a mark associated with active gene transcription and intergenic DNA methylation. In addition to a methyltransferase domain, NSD2 harbors two proline-tryptophan-tryptophan-proline (PWWP) domains and five...
Background
Currently, treatments for Alzheimer’s disease (AD) predominantly include acetylcholinesterase inhibitors, which address the symptomatic effects of the disease. The discovery of disease modifying interventions in the development and progression of AD are critical as there are currently no drugs or biologics which can elicit disease modify...
Canonical targeting of Polycomb repressive complex 1 (PRC1) to repress developmental genes is mediated by cell-type-specific, paralogous chromobox (CBX) proteins (CBX2, 4, 6, 7, and 8). Based on their central role in silencing and their dysregulation associated with human disease including cancer, CBX proteins are attractive targets for small-molec...
Introduction: The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the AMP-AD program.
Methods: A cheminformatics-driven effort enabled identification of existing small molecule modulators for many protein targets nominated by AMP-AD and suitable positive control compounds to be included in the set.
Results: We have...
Inhibition of MER receptor tyrosine kinase (MERTK) causes direct tumor cell killing and stimulation of the innate immune response. Therefore, MERTK has been identified as a therapeutic target in a wide variety of human tumors. Clinical trials targeting MERTK have recently initiated, however, none of these drugs are MERTK-specific. Herein, we presen...
NSD2 is the primary enzyme responsible for the dimethylation of lysine 36 of histone 3 (H3K36me2), a mark associated with active gene transcription and intergenic DNA methylation. In addition to a methyltransferase domain, NSD2 harbors two PWWP and five PHD domains believed to serve as chromatin reading modules, but their exact function in the regu...
Canonical targeting of Polycomb Repressive Complex 1 (PRC1) to repress developmental genes is mediated by cell type-specific, paralogous chromobox (CBX) proteins (CBX2, 4, 6, 7 and 8). Based on their central role in silencing and their misregulation associated with human disease including cancer, CBX proteins are attractive targets for small molecu...
Two critical steps in drug development are 1) the discovery of molecules that have the desired effects on a target, and 2) the optimization of such molecules into lead compounds with the required potency and pharmacokinetic properties for translation. DNA-encoded chemical libraries (DECLs) can nowadays yield hits with unprecedented ease, and lead-o...
Chromatin structure and function, and consequently cellular phenotype, is regulated in part by a network of chromatin-modifying enzymes that place post-translational modifications (PTMs) on histone tails. These marks serve as recruitment sites for other chromatin regulatory complexes that ‘read’ these PTMs. High-quality chemical probes that can blo...
While accurate quantitative prediction of ligand-protein binding affinity remains an elusive goal, high-affinity ligands to therapeutic targets are being designed through heuristic optimization of ligand-protein contacts. However, herein, through large-scale data mining and analyses, we demonstrate that a ligand’s binding can also be strongly affec...
Controlling which particular members of a large protein family are targeted by a drug is key to achieving a desired therapeutic response. In this study, we report a rational data-driven strategy for achieving restricted polypharmacology in the design of anti-tumor agents selectively targeting the TYRO3, AXL and MERTK (TAM) family tyrosine kinases....
Polycomb-directed repression of gene expression is frequently misregulated in human diseases. A quantitative and target-specific cellular assay was utilized to discover the first potent positive allosteric modulator (PAM) peptidomimetic, UNC4976, of nucleic acid binding by CBX7, a chromodomain methyl-lysine reader of Polycomb repressive complex 1....
Many common disease-causing mutations result in loss-of-function (LOF) of the proteins in which they occur. LOF mutations have proven recalcitrant to pharmacologic intervention, presenting a challenge for the development of targeted therapeutics. Polycomb repressive complex 2 (PRC2), which contains core subunits (EZH2, EED, and SUZ12), regulates ge...
Processing of substrates by enzymes can only be fully understood through their conformational dynamics; this is particularly true for the diphosphoinositol pentakisphosphate kinase PPIP5K2, an enzyme with critical roles in cell signaling and bioenergetic homeostasis. PPIP5K2 is remarkable for the reversible nature of its kinase activity, its unique...
As part of a program to explore the chemistry of β‐lactams and their derivatives, we prepared a focused set of benzazetidine, indoline, and indole heterocycles, as well as flexible unconstrained variations of the four‐membered heterocyclic compounds. These analogues mimic the three‐dimensional shape of cephalosporins but are not prone to covalent b...
DNA-encoded chemical libraries are increasingly used in pharmaceutical research because they enable the rapid discovery of synthetic protein ligands. Here we explored whether target-class focused DNA-encoded chemical libraries can be cost-effective tools to achieve robust screening productivity for a series of proteins. The study revealed that a DN...
The stereo configuration of compounds drawn in the original Figure 3A, Scheme S3, and Figure S7 and listed in the NMR data contained an error. The compounds in the corrected figure are drawn correctly as the S isomers. The synthesis section in the Supporting Information also contained this error, and it was corrected accordingly. (Figure Presented)...
Although all kinases share the same ATP binding pocket, subtle differences in the residues that form the pocket differentiate individual kinases’ affinity for ATP competitive inhibitors. We have found that by introducing a single methyl group, the selectivity of our MERTK inhibitors over another target, FLT3, was increased up to 1000-fold (compound...
CC–chemokine receptor 7 (CCR7) is a G protein–coupled receptor expressed on a variety of immune cells. CCR7 plays a critical role in the migration of lymphocytes into secondary lymphoid tissues. CCR7 expression, however, has been linked to numerous disease states. Due to its therapeutic relevance and absence of available CCR7 inhibitors, we underto...
Inositol hexakisphosphate kinases (IP6Ks) regulate a myriad of cellular processes, not only through their catalytic activity (which synthesizes InsP7, a multifunctional inositol pyrophosphate signaling molecule) but also through protein–protein interactions. To further study the enzymatic function and distinguish between these different mechanisms,...
Continuous exposure of a pancreatic cancer cell line MIA PaCa-2 (MiaS) to gemcitabine resulted in the formation of a gemcitabine-resistant subline (MiaR). In an effort to discover kinase inhibitors that inhibited MiaR growth, MiaR cells were exposed to kinase inhibitors (PKIS-1 library) in a 384-well screening format. Three compounds (UNC10112721A,...
Multivalent binding is an efficient means to enhance the affinity and specificity of chemical probes targeting multi-domain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, physical and structural characterization of bivalent binding encounters multiple technical difficulties...
The authors of the above paper retract this article due to concerns about the integrity of the data and the validity of the conclusions. The first author, Brandi M. Baughman, has admitted to the co-authors and the Office of Research Integrity at NIH that she falsified and/or fabricated data and text concerning Figs 2, 3, 4, 5, 6, 8, S1, S2, S3, S4,...
Macrocycles have attracted significant attention in drug discovery recently. In fact, a few de novo designed macrocyclic kinases inhibitors are currently in clinical trials with good potency and selectivity for their intended target. In this paper, we have successfully engaged a structure-based drug design approach to discover macrocyclic pyrimidin...
Pharmacological tools—‘chemical probes’—that intervene in cell signaling cascades are important for complementing genetically-based experimental approaches. Probe development frequently begins with a high-throughput screen (HTS) of a chemical library. Herein, we describe the design, validation, and implementation of the first HTS-compatible strateg...
Data from HTS of PPIP5K in a ‘reverse’ kinase assay.
A ‘reverse’ kinase assay was performed by incubating 30 nM PPIP5K with 70 nM 1,5-InsP8 and 0.1 mM ADP (i.e., its Km value) for 1 h at 25°C with individual molecules from the 5K kinase-focused library at a concentration of 13 μM. Next, firefly luciferase was added and we assayed the conversion of...
DMSO tolerance for HTS assay.
PPIP5K activity was recorded in HTS format by recording the production of ADP from ATP at the indicated concentrations of DMSO. The ADP signal was recorded at both 0.5 h (black bars) and 4 h (gray bars) after quenching the kinase reactions. Data represent the mean values ± SEM from three experiments.
(TIF)
Dose-response inhibition of PPIP5K1 by UNC10225354, UNC10225498, and UNC10112646.
Dose-response curves for the inhibition of PPIP5K1 by UNC10225354 (IC50 = 2.9 ± 1.2 μM), UNC10225498 (IC50 = 1.8 ± 0.9 μM), and UNC10112646 (IC50 = 7.3 ± 0.6 μM), Inhibition was measured using the HTRF procedures and conditions described in the Materials and Methods....
Structures and dose-response relationships for inhibitors of PPIP5Ks identified from the 5K kinase-focused library.
Chemical structures and dose-response curves for the inhibition of PPIP5K by (A) UNC10112561 (IC50 = 8.14 ± 0.05 μM), (B) UNC10112675 (IC50 >13 μM), (C) UNC10225044 (IC50 = 6.84 ± 0.78 μM), (D) UNC10225045 (IC50 >13 μM), (E) UNC102250...
Analysis by ITC of the interaction of UNC10225354 with PPIP5K.
The upper panel shows the raw data for heat output from the ligand/protein titrations; the lower panel shows the least squares fitting of the titration data assuming a single site binding model.
(TIF)
Clustering information for 5K library hits.
Hits produced by HTS of the 5K library fell into 10 different clusters of structural similarity.
(DOCX)
Mer tyrosine kinase (MerTK) is aberrantly elevated in various tumor cells and has a normal anti-inflammatory role in the innate immune system. Inhibition of MerTK may provide dual effects against these MerTK-expressing tumors through reducing cancer cell survival and redirecting the innate immune response. Recently, we have designed novel and poten...
Efforts to develop strategies for small molecule chemical probe discovery against the readers of the methyl-lysine (Kme) post-translational modification have been met with limited success. Targeted disruption of these protein-protein interactions via peptidomimetic inhibitor optimization is a promising alternative to small molecule hit discovery; h...
Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SB...
Lysine methylation is the most prolific posttranslational modification of histone proteins. Spatial arrangements of histone methylation marks (the histone code) mediate transcriptional activation or repression through the recruitment of methyllysine (KMe) effectors. The deregulation of the histone code is implicated in cancer and other diseases. Se...
FMS-like tyrosine kinase 3-targeted (FLT3-targeted) therapies have shown initial promise for the treatment of acute myeloid leukemia (AML) expressing FLT3-activating mutations; however, resistance emerges rapidly. Furthermore, limited options exist for the treatment of FLT3-independent AML, demonstrating the need for novel therapies that reduce tox...
The protozoan parasite Toxoplasma gondii secretes a family of serine-threonine protein kinases into its host cell in order to disrupt signaling and alter immune responses. One prominent secretory effector is the rhoptry protein 18 (ROP18), a serine-threonine kinase that phosphorylates immunity related GTPases (IRGs) and hence blocks interferon gamm...
Methyl-lysine (Kme) recognition domains play a central role in epigenetic regulation during cellular differentiation, development, and gene transcription with more than 200 known “reader” domains in the human proteome. We describe our target-class approach to ligand design and discovery for three cancer relevant members of this large family: L3MBTL...
Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) regulate a variety of cellular processes, including signaling through G protein-coupled receptors (GPCRs), endocytosis, exocytosis, and cell migration. These lipid kinases synthesize phosphatidylinositol 4,5-bisphosphate (PIP2) from phosphatidylinositol 4-phosphate [PI(4)P]. Because small-molecule...
In children, acute lymphoblastic leukemia (ALL) is treated with an intense regimen of chemotherapy yielding cure rates near 85%, yet significant hurdles remain, including decreasing toxicity and improving patient outcome in relapsed or refractory disease. Alternative strategies using available drugs are unlikely to provide significant improvements...
Accurate and affordable assessment of ligand-protein affinity for structure-based virtual screening (SB-VS) is a standing challenge. However, empirical post-docking filters based upon various types of structure-activity information may prove useful. Here, we introduce one such filter based upon three-dimensional Structural Protein-Ligand Interactio...
We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylatio...
The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug...
The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug...
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biologic subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyros...
Abnormal activation or overexpression of Mer receptor tyrosine kinase has been implicated in survival signaling and chemoresistance in many human cancers. Consequently, Mer is a promising novel cancer therapeutic target. A structure-based drug design approach using a pseudo-ring replacement strategy was developed and validated to discover a new fam...
We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are s...
Lysine methylation is a key epigenetic mark, the dysregulation of which is linked to many diseases. Small-molecule antagonism of methyl-lysine (Kme) binding proteins that recognize such epigenetic marks can improve our understanding of these regulatory mechanisms and potentially validate Kme binding proteins as drug-discovery targets. We previously...
DNA methylation and histone post-translational modifications (PTMs) represent two key epigenetic regulators of DNA information in chromatin. The faithful inheritance of DNA methylation is essential for normal mammalian development and long-term transcriptional silencing, and aberrant DNA methylation patterns are a hallmark of many cancers. Histone...
The intricate pattern of chemical modifications on DNA and histones, the
"histone code", is considered to be a key gene regulation factor. Multivalency
is seen by many as an essential instrument to transmit the "encoded"
information to the transcription machinery via multi-domain effector proteins
and chromatin-associated complexes. However, as exa...
Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. While significant progress has been made characterizing individual effector domains, the role of paired domains and how they function in a combinatorial fashion w...
We describe the discovery of UNC1215, a potent and selective chemical probe for the methyllysine (Kme) reading function of L3MBTL3, a member of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. UNC1215 binds L3MBTL3 with a K(d) of 120 nM, competitively displacing mono- or dimethyllysine-containing peptides,...
1317
Acute myelogenous leukemia (AML) is difficult to treat successfully in both adult and pediatric patients using conventional chemotherapy. Mutated or aberrantly expressed proteins on the cell surface of myeloblasts provide a focus for targeted therapy which could potentially augment therapeutic outcome, decrease toxicity to normal tissues, and/...
2607
Introduction
Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Current chemotherapeutic regimens are associated with short- and long-term toxicities. Therefore, novel, less toxic therapies are needed. Mer receptor tyrosine kinase (RTK) is ectopically expressed in ALL cell lines and patient samples. Inhibit...
The human commensal pathogen Streptococcus pneumoniae expresses a number of virulence factors that promote serious pneumococcal diseases, resulting in significant morbidity and mortality worldwide. These virulence factors may give S. pneumoniae the capacity to escape immune defenses, resist antimicrobial agents, or a combination of both. Virulence...
IKKε and TBK1 are noncanonical IKK family members which regulate inflammatory signaling pathways and also play important roles in oncogenesis. However, few inhibitors of these kinases have been identified. While the substrate specificity of IKKε has recently been described, the substrate specificity of TBK1 is unknown, hindering the development of...
ATP Km determination for IKKα and IKKβ. Enzymatic reactions of A) IKKα and B) IKKβ were incubated at room temperature with 10 ATP concentrations varying from 333 µM to 0.017 µM in three fold dilutions. Reactions were sampled on the Caliper EZReader system at 9.35 minute intervals over a 3 hour period. Percent conversions were calculated from relati...
Questions
Questions (2)
Postdoc Research Associate - Kireev lab
The group of Computational Biophysics and Molecular design (Kireev lab) is looking for a creative scientist to develop and apply novel techniques for Computer-Aided Drug Design. The major focus will be on artificial intelligence, structure-based, and molecular simulation approaches. You will provide a major contribution to collaborative translational projects in the Center for Integrative Chemical Biology and Drug Discovery (CICBDD). Therapeutic areas include cancer, aging, and neurologic disorders and involve innovative biomolecular targets.
Advanced knowledge and skills in deep learning, data processing, and structure-based approaches would be a significant advantage. Experience in statistical physics, thermodynamics, molecular simulations, chemoinformatics, and general molecular modeling will be highly appreciated. You are expected to have a broad interest in biomedical sciences. Specific skills include simulation and modeling software (Gromacs, NAMD, Shrodinger suite), programming (C++ or Python), data mining, and machine learning (Pipeline Pilot, R, Matlab, TensorFlow). You must display outstanding motivation and commitment to research in a fast-moving and competitive field. Excellent personal skills and the ability to work in a multidisciplinary team setting are essential.
Interested candidates apply online at,
https://unc.peopleadmin.com/postings/188932 along with your CV and a list of at least three professional references with their full contact information.
More Information on Dr. Kireev and his group’s research: https://pharmacy.unc.edu/directory/kireev/ or https://www.researchgate.net/profile/Dmitri_Kireev
