Constant pH molecular dynamics (MD) simulations sample protonation states on the fly
according to the conformational environment and user specified pH conditions; however, the …

Predictive modeling and understanding of chemical warhead reactivities have the potential
to accelerate targeted covalent drug discovery. Recently, the carbanion formation free …

Like temperature and pressure, solution pH is an important environmental variable in
biomolecular simulations. Virtually all proteins depend on pH to maintain their structure and …

Purpose Over the last few years, covalent fragment-based drug discovery has gained
significant importance. Thus, striving for more warhead diversity, we conceived a library …

This review outlines the role of electrostatics in computational molecular biophysics and its
implication in altering wild-type characteristics of biological macromolecules, and thus the …

The ERK pathway is one of the most important signaling cascades involved in
tumorigenesis. So far, eight noncovalent inhibitors of RAF and MEK kinases in the ERK …

Covalent drug design is an important component in drug discovery. Traditional drugs
interact with their target in a reversible equilibrium, while irreversible covalent drugs …

Abstract Interleukin-1 receptor-associated kinase 4 (IRAK4) is a vital protein involved in Toll-
like and interleukin-1 receptor signal transduction. Several studies have reported regarding …

Machine learning (ML) identification of covalently ligandable sites may accelerate targeted
covalent inhibitor design and help expand the druggable proteome space. Here, we report …

Acrylamides are the most commonly used warheads of targeted covalent inhibitors (TCIs)
directed at cysteines; however, the reaction mechanisms of acrylamides in proteins remain …