DP/MM: A Hybrid Model for Zinc–Protein Interactions in Molecular Dynamics

Zinc-containing proteins are vital for many biological processes, yet accurately modeling them using classical force fields is hindered by complicated polarization and charge transfer effects. This study introduces DP/MM, a hybrid force field scheme that utilizes a deep potential model to correct the atomic forces of zinc ions and their coordinated atoms, elevating them from MM to QM levels of accuracy. Trained on the difference between MM and QM atomic forces across diverse zinc coordination groups, the DP/MM model faithfully reproduces structural characteristics of zinc coordination during simulations, such as the tetrahedral coordination of Cys4 and Cys3His1 groups. Furthermore, DP/MM allows water exchange in the zinc coordination environment. With its unique blend of accuracy, efficiency, flexibility, and transferability, DP/MM serves as a valuable tool for studying structures and dynamics of zinc-containing proteins and also represents a pioneering approach in the evolving landscape of machine learning potentials for molecular modeling

DP/MM: A Hybrid Model for Zinc–Protein Interactions in Molecular Dynamics

Zinc-containing proteins are vital for many biological processes, yet accurately modeling them using classical force fields is hindered by complicated polarization and charge transfer effects. This study introduces DP/MM, a hybrid force field scheme that utilizes a deep potential model to correct the atomic forces of zinc ions and their coordinated atoms, elevating them from MM to QM levels of accuracy. Trained on the difference between MM and QM atomic forces across diverse zinc coordination groups, the DP/MM model faithfully reproduces structural characteristics of zinc coordination during simulations, such as the tetrahedral coordination of Cys4 and Cys3His1 groups. Furthermore, DP/MM allows water exchange in the zinc coordination environment. With its unique blend of accuracy, efficiency, flexibility, and transferability, DP/MM serves as a valuable tool for studying structures and dynamics of zinc-containing proteins and also represents a pioneering approach in the evolving landscape of machine learning potentials for molecular modeling

Additional file 1 of Comorbidities in congenital heart disease: different patterns in childhood and adulthood

Additional file 1

Binding Energy and Free Energy of Calcium Ion to Calmodulin EF-Hands with the Drude Polarizable Force Field

Calcium ions are important messenger molecules in cells, which bind calcium-binding proteins to trigger many biochemical processes. We constructed four model systems, each containing one EF-hand loop of calmodulin with one calcium ion bound, and investigated the binding energy and free energy of Ca2+ by the quantum mechanics symmetry-adapted perturbation theory (SAPT) method and the molecular mechanics with the additive CHARMM36m (C36m) and the polarizable Drude force fields (FFs). Our results show that the explicit introduction of polarizability in the Drude not only yields considerably improved agreement with the binding energy calculated from the SAPT method but is also able to capture each component of the binding energies including electrostatic, induction, exchange, and dispersion terms. However, binding free energies computed with the Drude and the C36m FFs both deviated significantly from the experimental measurements. Detailed analysis indicated that one of main reasons might be that the strong interactions between Ca2+ and the side chain nitrogen of Asn/Gln in the Drude FF caused the distorted coordination geometries of calcium. Our work illustrated the importance of polarization in modeling ion–protein interactions and the difficulty in generating accurate and balanced FF models to represent the polarization effects

sj-docx-2-inq-10.1177_00469580231224345 – Supplemental material for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study

Supplemental material, sj-docx-2-inq-10.1177_00469580231224345 for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study by Shangren Qin, Mengqiu Zhou, Yenuan Cheng, Junjie Zhao and Ye Ding in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

sj-docx-7-inq-10.1177_00469580231224345 – Supplemental material for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study

Supplemental material, sj-docx-7-inq-10.1177_00469580231224345 for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study by Shangren Qin, Mengqiu Zhou, Yenuan Cheng, Junjie Zhao and Ye Ding in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

sj-docx-5-inq-10.1177_00469580231224345 – Supplemental material for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study

Supplemental material, sj-docx-5-inq-10.1177_00469580231224345 for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study by Shangren Qin, Mengqiu Zhou, Yenuan Cheng, Junjie Zhao and Ye Ding in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

sj-docx-4-inq-10.1177_00469580231224345 – Supplemental material for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study

Supplemental material, sj-docx-4-inq-10.1177_00469580231224345 for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study by Shangren Qin, Mengqiu Zhou, Yenuan Cheng, Junjie Zhao and Ye Ding in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

sj-docx-6-inq-10.1177_00469580231224345 – Supplemental material for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study

Supplemental material, sj-docx-6-inq-10.1177_00469580231224345 for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study by Shangren Qin, Mengqiu Zhou, Yenuan Cheng, Junjie Zhao and Ye Ding in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

sj-docx-1-inq-10.1177_00469580231224345 – Supplemental material for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study

Supplemental material, sj-docx-1-inq-10.1177_00469580231224345 for Choice Preference of Middle-Aged and Elderly People on Integrated Medical Services and Elderly Care Model: A Cross-Sectional Study by Shangren Qin, Mengqiu Zhou, Yenuan Cheng, Junjie Zhao and Ye Ding in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p