Selective elimination of interactions

A method for assessing thermodynamic contributions to ligand binding with application to rhinovirus antivirals

Wan F. Lau, Bernard Pettitt

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A new method for evaluating the free energy of various physical interactions, such as hydrogen-bond, electrostatic, or van der Waals interactions, is presented. Rather than destroying or creating whole groups, selective (pairwise) interactions are eliminated from the total potential energy and the energy difference with the fully interacting system is evaluated. The exponential ensemble average of such an energy difference is then directly related to the corresponding free energy difference. This procedure is then applied to a rather large protein-ligand system involving the coat proteins of a human rhinovirus and an antiviral ligand. The results seem to indicate that a particular bent hydrogen bond between the ligand and protein system may not be favorable for binding. The method presented gives an estimate of the hydrogen bond free energy contribution with an available trajectory that was previously computed without the expenditure of sizeable computational resources such as recomputing a trajectory. This procedure is effective and efficient for computing the free energy for a given type of physical interaction. It can be used for calculating the binding energy differences for various interactions which can be used to guide the search for isosoluble synthetic targets.

Original languageEnglish (US)
Pages (from-to)2542-2547
Number of pages6
JournalJournal of Medicinal Chemistry
Volume32
Issue number12
StatePublished - 1989
Externally publishedYes

Fingerprint

Rhinovirus
Thermodynamics
Free energy
Antiviral Agents
Ligands
Hydrogen
Hydrogen bonds
Trajectories
Capsid Proteins
Health Expenditures
Potential energy
Binding energy
Static Electricity
Electrostatics
Proteins

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

@article{0bd934701e5340409c266272606ebaa9,
title = "Selective elimination of interactions: A method for assessing thermodynamic contributions to ligand binding with application to rhinovirus antivirals",
abstract = "A new method for evaluating the free energy of various physical interactions, such as hydrogen-bond, electrostatic, or van der Waals interactions, is presented. Rather than destroying or creating whole groups, selective (pairwise) interactions are eliminated from the total potential energy and the energy difference with the fully interacting system is evaluated. The exponential ensemble average of such an energy difference is then directly related to the corresponding free energy difference. This procedure is then applied to a rather large protein-ligand system involving the coat proteins of a human rhinovirus and an antiviral ligand. The results seem to indicate that a particular bent hydrogen bond between the ligand and protein system may not be favorable for binding. The method presented gives an estimate of the hydrogen bond free energy contribution with an available trajectory that was previously computed without the expenditure of sizeable computational resources such as recomputing a trajectory. This procedure is effective and efficient for computing the free energy for a given type of physical interaction. It can be used for calculating the binding energy differences for various interactions which can be used to guide the search for isosoluble synthetic targets.",
author = "Lau, {Wan F.} and Bernard Pettitt",
year = "1989",
language = "English (US)",
volume = "32",
pages = "2542--2547",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - Selective elimination of interactions

T2 - A method for assessing thermodynamic contributions to ligand binding with application to rhinovirus antivirals

AU - Lau, Wan F.

AU - Pettitt, Bernard

PY - 1989

Y1 - 1989

N2 - A new method for evaluating the free energy of various physical interactions, such as hydrogen-bond, electrostatic, or van der Waals interactions, is presented. Rather than destroying or creating whole groups, selective (pairwise) interactions are eliminated from the total potential energy and the energy difference with the fully interacting system is evaluated. The exponential ensemble average of such an energy difference is then directly related to the corresponding free energy difference. This procedure is then applied to a rather large protein-ligand system involving the coat proteins of a human rhinovirus and an antiviral ligand. The results seem to indicate that a particular bent hydrogen bond between the ligand and protein system may not be favorable for binding. The method presented gives an estimate of the hydrogen bond free energy contribution with an available trajectory that was previously computed without the expenditure of sizeable computational resources such as recomputing a trajectory. This procedure is effective and efficient for computing the free energy for a given type of physical interaction. It can be used for calculating the binding energy differences for various interactions which can be used to guide the search for isosoluble synthetic targets.

AB - A new method for evaluating the free energy of various physical interactions, such as hydrogen-bond, electrostatic, or van der Waals interactions, is presented. Rather than destroying or creating whole groups, selective (pairwise) interactions are eliminated from the total potential energy and the energy difference with the fully interacting system is evaluated. The exponential ensemble average of such an energy difference is then directly related to the corresponding free energy difference. This procedure is then applied to a rather large protein-ligand system involving the coat proteins of a human rhinovirus and an antiviral ligand. The results seem to indicate that a particular bent hydrogen bond between the ligand and protein system may not be favorable for binding. The method presented gives an estimate of the hydrogen bond free energy contribution with an available trajectory that was previously computed without the expenditure of sizeable computational resources such as recomputing a trajectory. This procedure is effective and efficient for computing the free energy for a given type of physical interaction. It can be used for calculating the binding energy differences for various interactions which can be used to guide the search for isosoluble synthetic targets.

UR - http://www.scopus.com/inward/record.url?scp=0024377366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024377366&partnerID=8YFLogxK

M3 - Article

VL - 32

SP - 2542

EP - 2547

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 12

ER -