Enhanced Sampling

String method with swarms of trajectories applied to GPCR activation free energies

We use the string method with swarms of trajectories to efficiently derive the minimum free energy activation pathway of GPCRs in the presence and absence of an agonist ligands. We present a generalized protocol in which the critical parameters of the simulation method are selected automatically, significantly reducing the efforts required to carry out and optimize this kind of simulation study.

Temperature-enhanced methods to sample conformational ensemble of calmodulin

Calmodulin is a physiologically crucial Ca2+-sensing protein that regulates more than 300 target proteins. We apply temperature replica exchange (T-REMD) and replica exchange solute tempering (REST) to sample available states and evaluate the efficiency of T-REMD and REST compared to regular MD on Ca2+-bound and Ca2+-free calmodulin using accurate free energy landscape reconstruction techniques.

Recent publications:

Inference of calmodulin’s Ca²⁺-dependent free energy landscapes via Gaussian mixture model validation AM Westerlund, TJ Harpole, C Blau and L Delemotte, J Chem Theor Comp, DOI: 10.1021/acs.jctc.7b00346

Effect of Ca2+ on the promiscuous target-protein binding mechanism of calmodulin A Westerlund, L Delemotte, PloS Comp Biol, DOI: 10.1371/journal.pcbi.1006072

Conformational landscapes of membrane proteins delineated by enhanced sampling molecular dynamics simulations TJ Harpole, L Delemotte, BBA Biomem, DOI: 10.1016/j.bbamem.2017.10.033


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