J. Chem. Inf. Model. 2020
Most Read
Virtual high throughput screening (vHTS) in drug discovery is a powerful approach to identify hits: when applied successfully, it can be much faster and cheaper than experimental high-throughput screening approaches. However, mainstream vHTS tools have significant limitations: ligand-based methods depend on knowledge of existing chemical matter, while structure-based tools such as docking involve significant approximations…
SC ’19, November 17–22
The implementation of Molecular Dynamics (MD) on FPGAs has received substantial attention. Previous work, however, has consisted of either proof-of-concept implementations of components, usually the range-limited force; full systems, but with much of the work shared by the host CPU; or prototype demonstrations, e.g., using OpenCL, that neither implement a whole system nor have competitive…
J. Chem. Inf. Model. 2019, 59, 11, 4720–4728
When both the difference between two quantities and their individual values can be measured or computationally predicted, multiple quantities can be determined from the measurements or predictions of select individual quantities and select pairwise differences. These measurements and predictions form a network connecting the quantities through their differences. Here, I analyze the optimization of such…
J. Chem. Phys. 150, 154121 (2019)
One popular approach to incorporating experimental data into molecular simulations is to restrain the ensemble average of observables to their experimental values. Here, I derive equations for the equilibrium distributions generated by restrained ensemble simulations and the corresponding expected values of observables. My results suggest a method to restrain simulations so that they generate distributions…
J. Chem. Inf. Model. 2017, 57, 12, 2911–2937
Most ReadWidely Cited
Accurate in silico prediction of protein–ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently,…
Sci Rep 5, 16924
Inhibition of cancer-promoting kinases is an established therapeutic strategy for the treatment of many cancers, although resistance to kinase inhibitors is common. One way to overcome resistance is to target orthogonal cancer-promoting pathways. Bromo and Extra-Terminal (BET) domain proteins, which belong to the family of epigenetic readers, have recently emerged as promising therapeutic targets in…
J. Am. Chem. Soc. 2013, 135, 41, 15579–15584
The mechanism (or mechanisms) of enthalpy–entropy (H/S) compensation in protein–ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands—human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with…
PNAS November 1, 2011 108 (44) 17889-17894
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The hydrophobic effect—a rationalization of the insolubility of nonpolar molecules in water—is centrally important to biomolecular recognition. Despite extensive research devoted to the hydrophobic effect, its molecular mechanisms remain controversial, and there are still no reliably predictive models for its role in protein–ligand binding. Here we describe a particularly well-defined system of protein and ligands—carbonic…
