Cleves, Ann E. Johnson, Stephen R. Jain, Ajay N.
Published in
Journal of Computer-Aided Molecular Design
We introduce a new method for rapid computation of 3D molecular similarity that combines electrostatic field comparison with comparison of molecular surface-shape and directional hydrogen-bonding preferences (called “eSim”). Rather than employing heuristic “colors” or user-defined molecular feature types to represent conformation-dependent molecula...
Cardoso-Silva, Jonathan Papageorgiou, Lazaros G Tsoka, Sophia
Published in
Journal of computer-aided molecular design
Quantitative Structure-Activity Relationship (QSAR) models are critical in various areas of drug discovery, for example in lead optimisation and virtual screening. Recently, the need for models that are not only predictive but also interpretable has been highlighted. In this paper, a new methodology is proposed to build interpretable QSAR models by...
Orgován, Zoltán Ferenczy, György G Keserű, György M
Published in
Journal of computer-aided molecular design
Stabilizing unique receptor conformations, allosteric modulators of G-protein coupled receptors (GPCRs) might open novel treatment options due to their new pharmacological action, their enhanced specificity and selectivity in both binding and signaling. Ligand binding occurs at intrahelical allosteric sites and involves significant induced fit effe...
Roterman, Irena Dułak, Dawid Gadzała, Małgorzata Banach, Mateusz Konieczny, Leszek
Published in
Journal of computer-aided molecular design
The structure of the Aβ(11-42) amyloid available in PDB makes possible the molecular analysis of the specificity of amyloid formation. This molecule (PDB ID 2MVX) is the object of analysis. This work presents the outcome of in silico experiments involving various alternative conformations of the Aβ(11-42) sequence, providing clues as to the amylodo...
Jain, Ajay N Cleves, Ann E Gao, Qi Wang, Xiao Liu, Yizhou Sherer, Edward C Reibarkh, Mikhail Y
Published in
Journal of computer-aided molecular design
ForceGen is a template-free, non-stochastic approach for 2D to 3D structure generation and conformational elaboration for small molecules, including both non-macrocycles and macrocycles. For conformational search of non-macrocycles, ForceGen is both faster and more accurate than the best of all tested methods on a very large, independently curated ...
Yau, Mei Qian Emtage, Abigail L. Chan, Nathaniel J. Y. Doughty, Stephen W. Loo, Jason S. E.
Published in
Journal of Computer-Aided Molecular Design
The recent expansion of GPCR crystal structures provides the opportunity to assess the performance of structure-based drug design methods for the GPCR superfamily. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA)-based methods are commonly used for binding affinity prediction, as they provide an intermediate compromise of speed and accu...
Vu, Oanh Mendenhall, Jeffrey Altarawy, Doaa Meiler, Jens
Published in
Journal of Computer-Aided Molecular Design
Comparing fragment based molecular fingerprints of drug-like molecules is one of the most robust and frequently used approaches in computer-assisted drug discovery. Molprint2D, a popular atom environment (AE) descriptor, yielded the best enrichment of active compounds across a diverse set of targets in a recent large-scale study. We present here BC...
Jiang, Cheng-Shi Ge, Yong-Xi Cheng, Zhi-Qiang Song, Jia-Li Wang, Yin-Yin Zhu, Kongkai Zhang, Hua
Published in
Journal of Computer-Aided Molecular Design
Although the mechanism of Alzheimer’s disease (AD) is still not fully understood, the development of multifunctional AChE inhibitors remains a research focus for AD treatment. In this study, 48 AChE candidate inhibitors were picked out from SPECS database through a pharmacophore- and molecular docking-based virtual screening. The biological evaluat...
Raza, Saad Ranaghan, Kara E. van der Kamp, Marc W. Woods, Christopher J. Mulholland, Adrian J. Azam, Syed Sikander
Published in
Journal of Computer-Aided Molecular Design
Kallikrein-8, a serine protease, is a target for structure-based drug design due to its therapeutic potential in treating Alzheimer’s disease and is also useful as a biomarker in ovarian cancer. We present a binding assessment of ligands to kallikrein-8 using a residue-wise decomposition of the binding energy. Binding of four putative inhibitors of...
Hu, Xin Zhang, Ya-Qin Lee, Olivia W. Liu, Li Tang, Manshu Lai, Kent Boxer, Matthew B. Hall, Matthew D. Shen, Min
Published in
Journal of Computer-Aided Molecular Design
Classic Galactosemia is a potentially lethal autosomal recessive metabolic disorder caused by deficient galactose-1-phosphate uridyltransferase (GALT) that results in the buildup of galactose-1-phosphate (gal-1-p) in cells. Galactokinase (GALK1) is the enzyme responsible for converting galactose into gal-1-p. A pharmacological inhibitor of GALK1 is...
