Target–ligand binding affinity from single point enthalpy calculation and elemental composition

Literature Information

Publication Date 2023-11-03
DOI 10.1039/D3CP04483A
Impact Factor 3.676
Authors

Viktor Szél, Balázs Zoltán Zsidó, Norbert Jeszenői, Csaba Hetényi


View Original

Abstract

Reliable target–ligand binding thermodynamics data are essential for successful drug design and molecular engineering projects. Besides experimental methods, a number of theoretical approaches have been introduced for the generation of binding thermodynamics data. However, available approaches often neglect electronic effects or explicit water molecules influencing target–ligand interactions. To handle electronic effects within a reasonable time frame, we introduce a fast calculator QMH-L using a single target–ligand complex structure pre-optimized at the molecular mechanics level. QMH-L is composed of the semi-empirical quantum mechanics calculation of binding enthalpy with predicted explicit water molecules at the complex interface, and a simple descriptor based on the elemental composition of the ligand. QMH-L estimates the target–ligand binding free energy with a root mean square error (RMSE) of 0.94 kcal mol−1. The calculations also provide binding enthalpy values and they were compared with experimental binding thermodynamics data collected from the most reliable isothermal titration calorimetry studies of systems including various protein targets and challenging, large peptide ligands with a molecular weight of up to 2–3 thousand. The single point enthalpy calculations of QMH-L require modest computational resources and are based on short runs with open source and/or free software like Gromacs, Mopac, MobyWat, and Fragmenter. QMH-L can be applied for fast, automated scoring of drug candidates during a virtual screen, enthalpic engineering of new ligands or thermodynamic explanation of complex interactions.

Related Literature

Solvent effects on ion–receptor interactions in the presence of an external electric field

Martin Novák, Cina Foroutan-Nejad

2016-10-19 Paper

DOI: 10.1039/C6CP05781K

Development of type-I/type-II hybrid dye sensitizer with both pyridyl group and catechol unit as anchoring group for type-I/type-II dye-sensitized solar cell

Yousuke Ooyama, Kensuke Furue, Toshiaki Enoki, Masahiro Kanda, Yohei Adachi, Joji Ohshita

2016-10-21 Paper

DOI: 10.1039/C6CP06513A

Inside back cover

Cover

DOI: 10.1039/C6CP90259F

Extraordinary stability of hemocyanins from L. polyphemus and E. californicum studied using infrared spectroscopy from 294 to 20 K

Mireille Khalil, Zahia Boubegtiten-Fezoua, Nadja Hellmann, Petra Hellwig

2016-09-22 Paper

DOI: 10.1039/C6CP03510H

Toward a modular multi-material nanoparticle synthesis and assembly strategy via bionanocombinatorics: bifunctional peptides for linking Au and Ag nanomaterials

J. Pablo Palafox-Hernandez, Yue Li, Chang-Keun Lim, Taylor J. Woehl, Nicholas M. Bedford, Soenke Seifert, Mark T. Swihart, Paras N. Prasad, Tiffany R. Walsh, Marc R. Knecht

2016-10-19 Paper

DOI: 10.1039/C6CP06135D

Effects of extending the π-conjugation of the acetylide ligand on the photophysics and reverse saturable absorption of Pt(ii) bipyridine bisacetylide complexes

Taotao Lu, Chengzhe Wang, Levi Lystrom, Chengkui Pei, Svetlana Kilina, Wenfang Sun

2016-09-19 Paper

DOI: 10.1039/C6CP02628A

Crystal structures and superconductivity of technetium hydrides under pressure

Xiaofeng Li, Hanyu Liu, Feng Peng

2016-09-27 Paper

DOI: 10.1039/C6CP05702K

Growth mechanism of Ge-doped CZTSSe thin film by sputtering method and solar cells

Jinze Li, Jieyi Chen, Jiale Yang

2016-09-27 Paper

DOI: 10.1039/C6CP05671G

Optical properties of acene molecules and pentacene crystal from the many-body Green's function method

Xia Leng, Jin Feng, Tingwei Chen, Chengbu Liu, Yuchen Ma

2016-10-18 Paper

DOI: 10.1039/C6CP05902C

You might also like

Compound Q&A

Are there alternatives to 1-(4-Chlorophenyl)-N-hydroxymethanimine (CAS: 3848-36-0) in synthesis?

When considering alternatives to 1-(4-Chlorophenyl)-N-hydroxymethanimine (CAS: 3...

3848-36-01-(4-Chlorophenyl)-N...
Compound Q&A

How is 3-(4-Bromophenyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole (CAS: 419553-16-5) typically synthesized?

3-(4-Bromophenyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole is synthesized through a m...

419553-16-53-(4-Bromophenyl)-5-...
Compound Q&A

How is 5-Chloro-2-(4-chlorophenyl)-4-methyl-6-[3-(1-piperidinyl)propoxy]pyrimidine (CAS: 1639220-19-1) typically synthesized?

5-Chloro-2-(4-chlorophenyl)-4-methyl-6-[3-(1-piperidinyl)propoxy]pyrimidine (CAS...

1639220-19-15-Chloro-2-(4-chloro...
Compound Q&A

What industries use 2-Chloro-4-(difluoromethoxy)pyridine (CAS: 1206978-15-5)?

2-Chloro-4-(difluoromethoxy)pyridine is used in the pharmaceutical industry for ...

1206978-15-52-Chloro-4-(difluoro...
Compound Q&A

What regulatory guidelines apply to 3-Chloro-6-methylpyridazine (CAS: 1121-79-5)?

3-Chloro-6-methylpyridazine (CAS: 1121-79-5) is classified under the Globally Ha...

1121-79-53-Chloro-6-methylpyr...
Compound Q&A

Are there alternatives to Methyl 4,5-dimethyl-2-nitrobenzoate in synthesis?

Several alternatives can be used in the synthesis of Methyl 4,5-dimethyl-2-nitro...

90922-74-0Methyl 4,5-dimethyl-...
Compound Q&A

Are there alternatives to (2E,2'E)-3,3'-(1,4-Phenylene)bisacrylaldehyde in synthesis?

Alternatives to (2E,2'E)-3,3'-(1,4-Phenylene)bisacrylaldehyde include other acry...

63405-68-5(2E,2'E)-3,3'-(1,4-P...
Compound Q&A

What is 3-Amino-5-chloropyridin-2-ol hydrochloride (CAS: 1261906-29-9)?

3-Amino-5-chloropyridin-2-ol hydrochloride is an organic compound with the CAS n...

1261906-29-93-Amino-5-chloropyri...
Compound Q&A

What precautions should be taken when handling 6,7-Difluoro-2,3-dihydro-4H-chromen-4-one (CAS: 1092349-93-3)?

When handling 6,7-Difluoro-2,3-dihydro-4H-chromen-4-one, it is essential to wear...

1092349-93-36,7-Difluoro-2,3-dih...

Source Journal

Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
CiteScore: 5.5
Self-citation Rate: 10.3%
Articles per Year: 3036

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.

Recommended Compounds

Recommended Suppliers

Disclaimer
This page provides academic journal information for reference and research purposes only. We are not affiliated with any journal publishers and do not handle publication submissions. For publication-related inquiries, please contact the respective journal publishers directly.
If you notice any inaccuracies in the information displayed, please contact us at support@chemtradehub.com. We will promptly review and address your concerns.