TY - JOUR

T1 - Does the Composition of the Surrounding Solution Affect the Structure and Stability of the Protein Complex with a Ligand? A Molecular Dynamics Study

AU - Vedkal, A. V.

AU - Kadtsyn, E. D.

N1 - This work was performed as part of the State Assignment of the Ministry of Science and Higher Education of the Russian Federation for the Synchrotron Radiation Facility–Siberian Circular Photon Source “SKlF” of the Boreskov Institute of Catalysis, Siberian Branch, Russian Academy of Sciences (FWUR-2024-0040). Vedkal, A. V. Does the Composition of the Surrounding Solution Affect the Structure and Stability of the Protein Complex with a Ligand? A Molecular Dynamics Study / A. V. Vedkal, E. D. Kadtsyn // Journal of Structural Chemistry. – 2025. – Vol. 66, No. 9. – P. 1959-1976. – DOI 10.1134/S0022476625090185.

PY - 2025/10/9

Y1 - 2025/10/9

N2 - Abstract: The 3D structure of proteins and protein–ligand complexes is determined by protein crystallography methods. In order to make the protein precipitate and prepare a complex, additional substances, including cosolvents, are added to the solution during the crystallization. However the presence of such additives can affect the structure of the protein and/or the complex, so that the XRD result will differ markedly from the structure of the complex in water and in physiological conditions. In the present study, we verify the presence of such influence on the example of a dimer of the SARS-Cov-2 main protease and a ligand exhibiting activity against SARS-CoV-2. An MD simulation of the complex in water and in 5% and 10% solutions of DMSO and dioxane in water is presented. It is shown that changes in the environment do not affect the structure of the protease dimer, but do significantly affect the interaction of the protein with the ligand. The sites of stable ligand bonding depend on the specific environment the complex is placed in. Thus, protein crystallography data should be treated very carefully: results obtained for one medium will not be necessarily true for another medium of a different composition.

AB - Abstract: The 3D structure of proteins and protein–ligand complexes is determined by protein crystallography methods. In order to make the protein precipitate and prepare a complex, additional substances, including cosolvents, are added to the solution during the crystallization. However the presence of such additives can affect the structure of the protein and/or the complex, so that the XRD result will differ markedly from the structure of the complex in water and in physiological conditions. In the present study, we verify the presence of such influence on the example of a dimer of the SARS-Cov-2 main protease and a ligand exhibiting activity against SARS-CoV-2. An MD simulation of the complex in water and in 5% and 10% solutions of DMSO and dioxane in water is presented. It is shown that changes in the environment do not affect the structure of the protease dimer, but do significantly affect the interaction of the protein with the ligand. The sites of stable ligand bonding depend on the specific environment the complex is placed in. Thus, protein crystallography data should be treated very carefully: results obtained for one medium will not be necessarily true for another medium of a different composition.

KW - DMSO

KW - SARS-CoV-2, Mpro

KW - dioxane

KW - medium crystallization

KW - molecular dynamics simulation

KW - protein crystallization

KW - protein–ligand complexes

UR - https://www.mendeley.com/catalogue/adf1e4a3-c2a6-3e5e-89a7-9845fab58f52/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105018645903&origin=inward

UR - https://www.elibrary.ru/item.asp?id=83009114

U2 - 10.1134/S0022476625090185

DO - 10.1134/S0022476625090185

M3 - Article

VL - 66

SP - 1959

EP - 1976

JO - Journal of Structural Chemistry

JF - Journal of Structural Chemistry

SN - 0022-4766

IS - 9

ER -