Steven K. Albanese

Discovery of 2H-Pyrrolo[3,4- c ]pyridin-3-one Derivatives as Type-III c-MET Inhibitors Enabled by Free-Energy Perturbation Calculations

Éric Therrien, Shulu Feng, Katherine Amberg-Johnson, Nadim Shaikh et autres

The clinical emergence of diverse c-MET mutations with resistance to approved inhibitors has created an urgent demand for next-generation inhibitors with efficacy against c-MET-resistant mutations while maintaining c-MET wild-type (WT) potency, selectivity over other kinases, and brain penetration. Here, we report a …

us (code pays fourni par la source)

Structure-Based Discovery of Imidazo[4,5- c ]pyridine SARM1 Modulators Showing Paradoxical Activation

Steven K. Albanese, Brittany E. Hopkins, Andrea M. Olland, Alexis Fairman et autres

.

us, de (code pays fourni par la source)

Accelerating Lead Optimization away from Anti-Targets: Navigating the Structural Complexity of Promiscuous ADMET Proteins

Howook Hwang, Mee Y. Shelley, Andrew Placzek, Kevin R. DeMarco et autres

The development of a small-molecule suitable for clinical use involves optimization of ligand binding to an identified target protein but also frequently the reduction of binding to a variety of anti-target proteins known to pose translational risk. These anti-targets, often referred to …

us, gb (code pays fourni par la source)

Structurally Enabling ADMET Anti-Targets via Induced Fit Docking and Free Energy Perturbation

Howook Hwang, Mee Y. Shelley, Andrew Placzek, Kevin R. DeMarco et autres

The development of a small-molecule suitable for clinical use involves optimization of ligand binding to an identified target protein but also frequently the reduction of binding to a variety of anti-target proteins known to pose translational risk. These anti-targets, often referred to …

us, gb (code pays fourni par la source)

Structurally Enabling ADMET Anti-Targets via Induced Fit Docking and Free Energy Perturbation

Howook Hwang, Mee Y. Shelley, Andrew Placzek, Kevin R. DeMarco et autres

The development of a small-molecule suitable for clinical use involves optimization of ligand binding to an identified target protein but also frequently the reduction of binding to a variety of anti-target proteins known to pose translational risk. These anti-targets, often referred to …

us, gb (code pays fourni par la source)

Predicting Resistance to Small Molecule Kinase Inhibitors

Anu Nagarajan, Katherine Amberg-Johnson, Evan Paull, Kunling Huang et autres

Drug resistance is a critical challenge in treating diseases like cancer and infectious disease. This study presents a novel computational workflow for predicting on-target resistance mutations to small molecule inhibitors (SMIs). The approach integrates genetic models with alchemical free energy perturbation (FEP+) …

us (code pays fourni par la source)

Predicting resistance to small molecule kinase inhibitors

Anu Nagarajan, Katherine Amberg-Johnson, Evan Paull, Kunling Huang et autres

Drug resistance is a critical challenge in treating diseases like cancer and infectious disease. This study presents a novel computational workflow for predicting on-target resistance mutations to small molecule inhibitors (SMIs). The approach integrates genetic models with alchemical free energy perturbation (FEP+) …

us (code pays fourni par la source)

OPLS5: Addition of Polarizability and Improved Treatment of Metals

Wolfgang Damm, Steven Dajnowicz, Delaram Ghoreishi, Yalun Yu et autres

We report on the development and validation of the OPLS5 force field. OPLS5 further extends the accuracy of our previous model (OPLS4) with the addition of explicit polarization to improve model accuracy for molecular ions and cation-pi interactions. OPLS5 also includes advances …

us (code pays fourni par la source)

The maximal and current accuracy of rigorous protein-ligand binding free energy calculations

Gregory A. Ross, Chao Tsang Lu, Guido Scarabelli, Steven K. Albanese et autres

Computational techniques can speed up the identification of hits and accelerate the development of candidate molecules for drug discovery. Among techniques for predicting relative binding affinities, the most consistently accurate is free energy perturbation (FEP), a class of rigorous physics-based methods. However, …

us (code pays fourni par la source)

The maximal and current accuracy of rigorous protein-ligand binding free energy calculations

Gregory A. Ross, Chao Tsang Lu, Guido Scarabelli, Steven K. Albanese et autres

It is now well recognized that computational techniques can greatly speed up the identification of hits and accelerate the optimization of such hits to lead series and development candidate molecules. In particular, a class of rigorous physics-based methods known as free energy …

us (code pays fourni par la source)

Discovery and characterization of novel inhibitors of CTP synthase 1 (CTPS1) for the treatment of autoimmune and inflammatory disease

Joshua J. McElwee, Neelu Kaila, Samantha T. Carreiro, Sheetal Kumar et autres

Abstract The de novo pyrimidine biosynthetic pathway is an inducible cellular program which allows the rapid synthesis of pyrimidine nucleotides in proliferating cells, and the final rate-limiting step is catalyzed by cytidine triphosphate synthase (CTPS1 or CTPS2). A CTPS1 loss-of-function mutation in …

it, gb, us (code pays fourni par la source)

The maximal and current accuracy of rigorous protein-ligand binding free energy calculations

Gregory A. Ross, Chao Tsang Lu, Guido Scarabelli, Steven K. Albanese et autres

us (code pays fourni par la source)