Finding multiple reaction pathways of ligand unbinding

Finding multiple reaction pathways via global optimization of action

Global searching for reaction pathways is a long-standing challenge in computational chemistry and biology. Most existing approaches perform only local searches due to computational complexity. Here we present a computational approach, Action-CSA, to find multiple diverse reaction pathways connecting fixed initial and final states through global optimization of the Onsager-Machlup action using ...

How wet should be the reaction coordinate for ligand unbinding?

We use a recently proposed method called Spectral Gap Optimization of Order Parameters (SGOOP) [P. Tiwary and B. J. Berne, Proc. Natl. Acad. Sci. U. S. A. 113, 2839 (2016)], to determine an optimal 1-dimensional reaction coordinate (RC) for the unbinding of a bucky-ball from a pocket in explicit water. This RC is estimated as a linear combination of the multiple available order parameters that ...

Kinetics of protein-ligand unbinding: Predicting pathways, rates, and rate-limiting steps.

The ability to predict the mechanisms and the associated rate constants of protein-ligand unbinding is of great practical importance in drug design. In this work we demonstrate how a recently introduced metadynamics-based approach allows exploration of the unbinding pathways, estimation of the rates, and determination of the rate-limiting steps in the paradigmatic case of the trypsin-benzamidin...

Ligand Unbinding from the Estrogen Receptor;

Finding Minimal Reaction Sets in Large Metabolic Pathways

In systems biology, identifying vital functions like glycolysis from a given metabolic pathway is important to understand living organisms. In this paper, we particularly focus on the problem of finding minimal sub-pathways producing target metabolites from source metabolites. We represent laws of biochemical reactions in propositional formulas and use a minimal model generator based on a state...