Potential Mean Force from Umbrella Sampling Simulations: What Can We Learn and What Is Missed?

Journal of Chemical Theory and Computation
Wanli YouChia-En A Chang

Abstract

Changes in free energy provide valuable information for molecular recognition, including both ligand-receptor binding thermodynamics and kinetics. Umbrella sampling (US), a widely used free energy calculation method, has long been used to explore the dissociation process of ligand-receptor systems and compute binding free energy. In existing publications, the binding free energy computed from the potential of mean force (PMF) with US simulation mostly yielded "ball park" values with experimental data. However, the computed PMF values are highly influenced by factors such as initial conformations and/or trajectories provided, the reaction coordinate, and sampling of conformational space in each US window. These critical factors have rarely been carefully studied. Here we used US to study the guest aspirin and 1-butanol dissociation processes of β-cyclodextrin (β-CD) and an inhibitor SB2 dissociation from a p38α mitogen-activated protein kinase (MAPK) complex. For β-CD, we used three different β-CD conformations to generate the dissociation path with US windows. For p38α, we generated the dissociation pathway by using accelerated molecular dynamics followed by conformational relaxing with short conventional MD, steered MD, and ma...Continue Reading

References

Oct 1, 1998·Structure·Z WangE J Goldsmith
Jan 5, 2002·Progress in Medicinal Chemistry·J L AdamsJ C Lee
Feb 19, 2002·Chemical Reviews·Mikhail V. Rekharsky, Yoshihisa Inoue
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Morten Ø JensenKlaus Schulten
May 23, 2002·Cell·Morgan Huse, John Kuriyan
Sep 3, 2003·Nature Reviews. Drug Discovery·Sanjay KumarJohn C Lee
Jul 23, 2004·The Journal of Chemical Physics·Donald HamelbergJ Andrew McCammon
Dec 24, 2005·Angewandte Chemie·Martin VogtherrHarald Schwalbe
Feb 4, 2006·Current Topics in Medicinal Chemistry·Christian PeiferStefan Laufer
Mar 3, 2006·The Journal of Physical Chemistry. B·Takanori FukahoriSadakatsu Nishikawa
Feb 17, 2007·The Journal of Chemical Physics·Davide BranduardiMichele Parrinello
May 8, 2007·Biochimica Et Biophysica Acta·Ana Cuenda, Simon Rousseau
Aug 28, 2007·Journal of Dental Research·J F SchindlerW G Smith
Dec 3, 2008·The Journal of Chemical Physics·Maria Mills, Ioan Andricioaei
Dec 3, 2008·The Journal of Chemical Physics·Michael R Shirts, John D Chodera
Feb 28, 2009·Nature Reviews. Drug Discovery·György M Keserü, Gergely M Makara
Oct 27, 2009·Expert Opinion on Investigational Drugs·Hae-Young YongAree Moon
May 9, 2008·Journal of Chemical Theory and Computation·William L Jorgensen, Laura L Thomas
Apr 7, 2010·Annual Review of Physical Chemistry·Alex Dickson, Aaron R Dinner
Nov 3, 2011·Journal of Chemical Theory and Computation·Ilja V Khavrutskii, Anders Wallqvist
Jul 4, 2012·Journal of Chemical Theory and Computation·Camilo Velez-Vega, Michael K Gilson
Mar 13, 2014·Expert Opinion on Therapeutic Patents·Stefanie Bühler, Stefan A Laufer
Sep 11, 2014·British Journal of Pharmacology·E D MartinM S Marber
Sep 24, 2014·The Journal of Physical Chemistry. B·Jeffrey ComerChristophe Chipot
Oct 21, 2014·Journal of Chemical Theory and Computation·Peng TaoBernard R Brooks
Sep 18, 2015·Cancer Research·Ana Igea, Angel R Nebreda
Nov 12, 2013·Journal of Chemical Theory and Computation·Danial Sabri Dashti, Adrian E Roitberg
Apr 14, 2009·Journal of Chemical Theory and Computation·Slimane DoudouRichard H Henchman
Jul 14, 2016·The Journal of Physical Chemistry. B·Sunhwan JoBenoît Roux
Jul 28, 2016·Molecular Simulation·Yinglong Miao, J Andrew McCammon
Sep 24, 2016·Journal of Computer-aided Molecular Design·Jian YinMichael K Gilson
Nov 5, 2016·Frontiers in Bioscience (Landmark Edition)·Zhiye TangChia-En A Chang
Jan 26, 2018·Frontiers in Molecular Biosciences·Changhao WangRay Luo

❮ Previous
Next ❯

Citations

Jan 28, 2020·Journal of Computer-aided Molecular Design·Andrea RizziJohn D Chodera
Nov 17, 2020·PLoS Computational Biology·Amir BitranEugene Shakhnovich
Jan 14, 2021·Journal of Biomolecular Structure & Dynamics·Khadijeh AhmadiHamid Madanchi
Aug 29, 2020·Journal of Chemical Theory and Computation·Hao LiuZheng Zheng
Apr 13, 2021·Journal of Biomechanics·Mohan YasodharababuArun K Nair
Nov 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jayvee R AbellaLydia E Kavraki
Jun 16, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Hung M LeAurora E Clark
Jun 18, 2021·Journal of Chemical Theory and Computation·Abhishek AcharyaUlrich Kleinekathöfer
Apr 24, 2020·Journal of Chemical Theory and Computation·Farzaneh JalalypourCanan Atilgan
Dec 10, 2020·Journal of Chemical Information and Modeling·Levente M MihalovitsGyörgy M Keserű
Feb 23, 2020·The Journal of Physical Chemistry. B·Shahidul M IslamPierre-Nicholas Roy
Jun 5, 2020·Journal of Chemical Theory and Computation·Sebastian Wingbermühle, Lars V Schäfer
Aug 22, 2020·Journal of the American Chemical Society·Cristina García-SimónXavi Ribas
Sep 25, 2021·Journal of Chemical Information and Modeling·Cristina González-FernándezInmaculada Ortiz
Sep 29, 2021·Journal of Biomolecular Structure & Dynamics·Bratin Kumar Das, Debashree Chakraborty
Nov 4, 2021·Expert Opinion on Drug Discovery·Qianqian ZhangHuanxiang Liu
Nov 20, 2021·Journal of Biomolecular Structure & Dynamics·Hanifeh Shariatifar, Alireza Farasat

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.