An Effective MM/GBSA Protocol for Absolute Binding Free Energy Calculations: A Case Study on SARS-CoV-2 Spike Protein and the Human ACE2 Receptor.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Negin Forouzesh, Nikita Mishra


The binding free energy calculation of protein-ligand complexes is necessary for research into virus-host interactions and the relevant applications in drug discovery. However, many current computational methods of such calculations are either inefficient or inaccurate in practice. Utilizing implicit solvent models in the molecular mechanics generalized Born surface area (MM/GBSA) framework allows for efficient calculations without significant loss of accuracy. Here, GBNSR6, a new flavor of the generalized Born model, is employed in the MM/GBSA framework for measuring the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor. A computational protocol is developed based on the widely studied Ras-Raf complex, which has similar binding free energy to SARS-CoV-2/ACE2. Two options for representing the dielectric boundary of the complexes are evaluated: one based on the standard Bondi radii and the other based on a newly developed set of atomic radii (OPT1), optimized specifically for protein-ligand binding. Predictions based on the two radii sets provide upper and lower bounds on the experimental references: -14.7(ΔGbindBondi)<-10.6(ΔGbindExp.)<-4.1(ΔGbindOPT1) kcal/mol. The consensus estimates of the two bou...Continue Reading


Apr 9, 2001·The Journal of Biological Chemistry·M G RudolphC Herrmann
Jan 16, 2002·Drug Discovery Today·Gisbert Schneider, Hans-Joachim Böhm
Dec 4, 2003·Journal of Computational Chemistry·Holger Gohlke, David A Case
Jan 22, 2004·Journal of Computational Chemistry·Emilio Gallicchio, Ronald M Levy
Mar 20, 2004·Science·William L Jorgensen
Apr 20, 2005·The Journal of Chemical Physics·Grigori SigalovAlexey Onufriev
Apr 8, 2006·The Journal of Chemical Physics·Grigori SigalovAlexey Onufriev
Nov 21, 2007·The Journal of Chemical Physics·John MonganAlexey Onufriev
Apr 30, 2008·Nucleic Acids Research·Sergey Lyskov, Jeffrey J Gray
Apr 23, 2009·The Journal of Physical Chemistry. a·Manjeera MantinaDonald G Truhlar
Jul 11, 2009·Chemical Reviews·Huan-Xiang Zhou, Michael K Gilson
Feb 26, 2011·Current Opinion in Structural Biology·John D ChoderaVijay S Pande
Jun 1, 2011·Nucleic Acids Research·Aurélien GrosdidierOlivier Michielin
Jul 24, 2012·Journal of Chemical Information and Modeling·Samuel GenhedenUlf Ryde
Mar 7, 2014·Journal of Computer-aided Molecular Design·Hari S MuddanaMichael K Gilson
Nov 18, 2014·The Journal of Physical Chemistry Letters·Saeed IzadiAlexey V Onufriev
Apr 4, 2015·Expert Opinion on Drug Discovery·Samuel Genheden, Ulf Ryde
Apr 29, 2015·Journal of Computational Chemistry·William J AllenRobert C Rizzo
May 1, 2014·Journal of Theoretical & Computational Chemistry·Alexey V Onufriev, Boris Aguilar
Aug 12, 2014·Journal of Chemical Theory and Computation·Nadine HomeyerHolger Gohlke
Jul 10, 2012·Journal of Chemical Theory and Computation·Boris Aguilar, Alexey V Onufriev
Sep 11, 2012·Journal of Chemical Theory and Computation·Bill R MillerAdrian E Roitberg
Sep 17, 2010·Molecular Informatics·Julien MichelJonathan W Essex
Feb 1, 2012·Molecular Informatics·Nadine Homeyer, Holger Gohlke
Dec 21, 2016·Journal of Chemical Information and Modeling·Ido Y Ben-ShalomHolger Gohlke
Aug 9, 2017·Journal of Chemical Information and Modeling·Negin ForouzeshAlexey V Onufriev
Jan 11, 2018·Chemical Reviews·Huan-Xiang Zhou, Xiaodong Pang
Jan 26, 2018·Frontiers in Molecular Biosciences·Changhao WangRay Luo
Jan 31, 2018·Journal of Chemical Theory and Computation·Saeed IzadiAlexey V Onufriev
Jun 16, 2018·Physical Chemistry Chemical Physics : PCCP·Adolfo B PomaPanagiotis E Theodorakis
Nov 12, 2018·Journal of Computer-aided Molecular Design·Andrea RizziJohn D Chodera
Mar 13, 2019·Annual Review of Biophysics·Alexey V Onufriev, David A Case
Jul 22, 2019·Trends in Pharmacological Sciences·Stefan HarrerJianying Hu
Sep 27, 2019·Journal of Computer-aided Molecular Design·Junjie ZouCarlos Simmerling
Nov 30, 2019·Journal of Computer-aided Molecular Design·Sukanya SasmalDavid L Mobley
Dec 25, 2019·Journal of Chemical Information and Modeling·Matías MartínezHoracio V Guzman
Jan 28, 2020·Biophysics and Physicobiology·Takahisa Yamato, Olivier Laprévote
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 24, 2020·Current Opinion in Structural Biology·Anita de Ruiter, Chris Oostenbrink

❮ Previous
Next ❯

Related Concepts

Trending Feeds


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.

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.

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.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies 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.


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.

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.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.