A5086410863- Computational Drug Discovery Methods
- X-ray Diffraction in Crystallography
- Protein Structure and Dynamics
- Crystallization and Solubility Studies
- Machine Learning in Materials Science
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Advanced Data Storage Technologies
- Various Chemistry Research Topics
- Parallel Computing and Optimization Techniques
- DNA and Nucleic Acid Chemistry
- Simulation Techniques and Applications
- Bacterial Genetics and Biotechnology
- Gene Regulatory Network Analysis
- Statistical Methods in Clinical Trials
- Genomics and Chromatin Dynamics
- Melanoma and MAPK Pathways
- Magnetism in coordination complexes
- Metal complexes synthesis and properties
- Mechanisms of cancer metastasis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Metal-Organic Frameworks: Synthesis and Applications
Carnegie Mellon University
2023-2025
University of Pittsburgh
2018
Using diverse building blocks, such as different heterometallic clusters, in metal-organic framework (MOF) syntheses greatly increases MOF complexity and leads to emergent synergistic properties. However, applying reticular chemistry involving more than two molecular blocks is challenging there limited progress this area. We are therefore motivated develop a strategy for achieving systematic differential control over the coordination of multiple metals MOFs. Herein, we report design...
In this work, we combined Deep Docking and free energy MD simulations for the in silico screening experimental validation potential inhibitors of leucine rich repeat kinase 2 (LRRK2) targeting WD40 (WDR) domain.
The CACHE challenges are a series of prospective benchmarking exercises to evaluate progress in the field computational hit-finding. Here we report results inaugural challenge which 23 teams each selected up 100 commercially available compounds that they predicted would bind WDR domain Parkinson's disease target LRRK2, with no known ligand and only an apo structure PDB. lack binding data presumably low druggability is hit finding methods. Of 1955 molecules by participants Round 1 challenge,...
Computing the free energy of protein-ligand binding by employing molecular dynamics (MD) simulations is becoming a valuable tool in early stages drug discovery. However, cost and complexity such are often prohibitive for high-throughput studies. We present an automated workflow thermodynamic integration scheme with “on-the-fly” optimization computational resource allocation each λ-window both relative absolute simulations. This iterative utilizes automatic equilibration detection convergence...
Computing the free energy of protein-ligand binding by employing molecular dynamics (MD) simulations is becoming a valuable tool in early stages drug discovery. However, cost and complexity such are often prohibitive for high-throughput studies. We present an automated workflow thermodynamic integration scheme with "on-the-fly" optimization computational resource allocation each λ-window both relative absolute simulations. This iterative utilizes automatic equilibration detection convergence...
The Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenge series is focused on identifying small molecule inhibitors protein targets using computational methods. Each challenge contains two phases, hit-finding and follow-up optimization, each which followed by experimental validation the predictions.. For CACHE #1, Leucine-Rich Repeat Kinase 2 (LRRK2) WD40 (WDR) domain was selected as target for in silico optimization. Mutations LRRK2 are most common genetic cause...
ABSTRACT The CACHE challenges are a series of prospective benchmarking exercises meant to evaluate progress in the field computational hit-finding. Here we report results inaugural #1 challenge which 23 teams each selected up 100 commercially available compounds that they predicted would bind WDR domain Parkinson’s disease target LRRK2, with no known ligand and only an apo structure PDB. lack binding data presumably low druggability is hit finding methods. Seventy-three 1955 procured...
The leucine-rich repeat kinase 2 (LRRK2) is the most mutated gene in familial Parkinson’s disease, whose mutations lead to pathogenic hallmarks of disease. LRRK2 WDR domain an understudied drug target for disease with no known inhibitors prior first phase Critical Assessment Computational Hit-Finding Experiments (CACHE) Challenge. CACHE challenges are designed attract state-of-the-art computational methods both hit-finding and optimization small molecule challenging protein targets. A unique...
Molecular dynamics simulations to compute protein small molecule binding free energies are becoming a valuable tool in the early stages of drug discovery. However, their cost and complexity often prohibitive for high-throughput studies. Herein, we present an automated workflow thermodynamic integration scheme with “on-the-fly” optimization computational resource allocation each λ-window both relative absolute energy simulations. This iterative utilizes automatic equilibration detection...
The Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenge is focused on identifying small molecule inhibitors protein targets using computational methods. For the CACHE #1, Leucine-Rich Repeat Kinase 2 (LRRK2) WD40 (WDR) domain was selected as target for in silico hit-finding and optimization. Mutations LRRK2 are most common genetic cause familial form Parkinson's disease. WDR an understudied drug with no known molecular inhibitors. We developed a framework...
Molecular dynamics simulations to compute protein small molecule binding free energies are becoming a valuable tool in the early stages of drug discovery. However, their cost and complexity often prohibitive for high-throughput studies. Herein, we present an automated workflow thermodynamic integration scheme with “on-the-fly” optimization computational resource allocation each λ-window both relative absolute energy simulations. This iterative utilizes automatic equilibration detection...