Computational tools to model halogen bonds in medicinal chemistry.

Ford, Melissa Coates; Ho, P. Shing

doi:10.1021/acs.jmedchem.5b00997

Cited by 143Crystallography and molecular interactionsComputational Drug Discovery MethodsAdvanced Chemical Physics Studies

Computational tools to model halogen bonds in medicinal chemistry.

Ford, Melissa Coates, Ho, P. Shing·2016·Journal of Medicinal Chemistry

DOI 10.1021/acs.jmedchem.5b00997

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Abstract

The use of halogens in therapeutics dates back to the earliest days of medicine when seaweed was used as a source of iodine to treat goiters. The incorporation of halogens to improve the potency of drugs is now fairly standard in medicinal chemistry. In the past decade, halogens have been recognized as direct participants in defining the affinity of inhibitors through a noncovalent interaction called the halogen bond or X-bond. Incorporating X-bonding into structure-based drug design requires computational models for the anisotropic distribution of charge and the nonspherical shape of halogens, which lead to their highly directional geometries and stabilizing energies. We review here current successes and challenges in developing computational methods to introduce X-bonding into lead compound discovery and optimization during drug development. This fast-growing field will push further development of more accurate and efficient computational tools to accelerate the exploitation of halogens in medicinal chemistry.

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Many studies have highlighted the influence of halogen bonds on enhancing binding affinity against several targets.
“Many studies have highlighted the influence of halogen bonds (X-bonds) on enhancing binding affinity against several targets and the computational methods developed so far (Desiraju et al., 2013; Ford and Ho, 2016).”
From Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges (2018) · cites this paper as Ford and Ho, 2016

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Authors: Ford, M. C., & Ho, P. S.
Affiliations: Colorado State University (US)
Corresponding author: Ho, P. Shing
ORCID: Ford, Melissa Coates
Ho, P. Shing
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2015-10-21
Volume: 59
Issue: 5
Pages: 1655-1670
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/acs.jmedchem.5b00997
OpenAlex: W2415942953
Cited by: 143
References: 116
Citations by year: 2026: 8 · 2025: 9 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 20 · 2018: 17 · 2017: 23 · 2016: 14
FWCI: 1.14
Type: journal article
Language: en
Open access: closed
Locations: Journal of Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Division of Chemistry (CHE-1152494)
Colorado State University
Topics: Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Crystallography and molecular interactions
Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
Keywords: halogen bonding, structure-based drug design, non-covalent interactions, lead optimization
MeSH terms: Chemistry, Pharmaceutical, Halogens, Humans, Models, Molecular, Quantum Theory, Drug Discovery

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Computational tools to model halogen bonds in medicinal chemistry.

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