scholarly journals Effective prediction of short hydrogen bonds in proteins via machine learning method

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengmin Zhou ◽  
Yuanhao Liu ◽  
Sijian Wang ◽  
Lu Wang
Keyword(s):  
Machine Learning ◽  
Hydrogen Bond ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Protein Structures ◽  
Decomposition Analysis ◽  
Energy Decomposition Analysis ◽  
Donor And Acceptor ◽  
Wide Range ◽  
Short Hydrogen Bonds

AbstractShort hydrogen bonds (SHBs), whose donor and acceptor heteroatoms lie within 2.7 Å, exhibit prominent quantum mechanical characters and are connected to a wide range of essential biomolecular processes. However, exact determination of the geometry and functional roles of SHBs requires a protein to be at atomic resolution. In this work, we analyze 1260 high-resolution peptide and protein structures from the Protein Data Bank and develop a boosting based machine learning model to predict the formation of SHBs between amino acids. This model, which we name as machine learning assisted prediction of short hydrogen bonds (MAPSHB), takes into account 21 structural, chemical and sequence features and their interaction effects and effectively categorizes each hydrogen bond in a protein to a short or normal hydrogen bond. The MAPSHB model reveals that the type of the donor amino acid plays a major role in determining the class of a hydrogen bond and that the side chain Tyr-Asp pair demonstrates a significant probability of forming a SHB. Combining electronic structure calculations and energy decomposition analysis, we elucidate how the interplay of competing intermolecular interactions stabilizes the Tyr-Asp SHBs more than other commonly observed combinations of amino acid side chains. The MAPSHB model, which is freely available on our web server, allows one to accurately and efficiently predict the presence of SHBs given a protein structure with moderate or low resolution and will facilitate the experimental and computational refinement of protein structures.

scholarly journals Intramolecular Hydrogen Bond Energy and Its Decomposition—O–H∙∙∙O Interactions

Crystals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 5
Author(s):  
Sławomir J. Grabowski
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Intramolecular Hydrogen Bond ◽  
Bond Energy ◽  
Decomposition Analysis ◽  
Energy Decomposition Analysis ◽  
Energy Decomposition ◽  
Intermolecular Hydrogen Bonds ◽  
Hydrogen Bond Energy ◽  
Intramolecular Hydrogen

The method to calculate the energy of intramolecular hydrogen bond is proposed and tested for a sample of malonaldehyde and its fluorine derivatives; the corresponding calculations were performed at the ωB97XD/aug-cc-pVTZ level. This method based on relationships found for related intermolecular hydrogen bonds is compared with other approaches which may be applied to estimate the intramolecular hydrogen bond energy. Particularly, methods based on the comparison of the system that contains the intramolecular hydrogen bond compared with corresponding conformations where such interaction does not occur are discussed. The function-based energy decomposition analysis, FB-EDA, of the intramolecular hydrogen bonds is also proposed here.

scholarly journals Evidence of sulfur centered hydrogen bond with sulfur atoms as a donor in aromatic thiols and aliphatic thiols on complexation with water using quantum mechanical methods

2021 ◽  
Author(s):  
Arnav Paul ◽  
Renjith Thomas
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Decomposition Analysis ◽  
Nbo Analysis ◽  
Energy Decomposition Analysis ◽  
Mechanical Methods ◽  
Aromatic Thiols ◽  
Density Delocalization ◽  
Aliphatic Thiols ◽  
Triple Excitation

It has been more than a century since the discovery of hydrogen bonds, but the knowledge about its impact on day to day life of people is getting enhanced even now. It has a pivotal role in the stabilization of various biomolecules and subsequent bioactivity. Sulfur cantered hydrogen bond (SCHB), which is a weak interaction, has attracted the attention of many scientists in the last few decades. In this work, we report the nature of the SCHB between aliphatic/aromatic thiols and water. B3LYP-D3(BJ) with cc-pVTZ level was used for modeling the hydrogen bonded thiol-water complexes. Domain-based local pair natural orbitals coupled-cluster theory with single, double, and perturbative triple excitation DLPNO-CCSD(T) method was used for local energy decomposition analysis. QTAIM analysis helped to examine hydrogen bonds, weak non-covalent interactions, and the various electron density delocalization. Natural Bond Orbital (NBO) analysis explains the reason for the sulfur atom being the H-bond donor. Second-order perturbation energy from NBO findings supports the data obtained by LED and AIM calculations. Aromatic thiols form stronger hydrogen bonds than aliphatic thiols. The effect of substituents was also explored by studying aromatic systems with electron-withdrawing groups and donating groups. EDG substituted have more vital interaction, and EWG substituted thiols form stronger S-H…O hydrogen bonds.

scholarly journals Unusual Spectroscopic and Electric Field Sensitivity of a Chromophore with Short Hydrogen Bond: GFP and PYP as Model Systems

2020 ◽  
Author(s):  
Chi-Yun Lin ◽  
Steven Boxer
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Electric Field ◽  
External Electric Field ◽  
Heavy Atom ◽  
Model Systems ◽  
Donor And Acceptor ◽  
Short Hydrogen Bond ◽  
Structural Methods ◽  
Short Hydrogen Bonds

<p> Short hydrogen bonds, with heavy-atom distances less than 2.7 Å, are believed to exhibit proton delocalization and their possible role in catalysis has been widely debated. While spectroscopic and/or structural methods are usually employed to study the degree of proton delocalization, ambiguities still arise and no direct information on the corresponding potential energy surface is obtained. Here we apply an external electric field to perturb the short hydrogen bond(s) within a collection of green fluorescent protein S65T/H148D variants and photoactive yellow protein mutants, where the chromophore participates in the short hydrogen bond(s) and serves as an optical probe of the proton position. As the proton is charged, its position may shift in response to the external electric field, and the chromophore’s electronic absorption can thus reflect the ease of proton transfer. The results suggest that low-barrier hydrogen bonds are not present within these proteins even when proton affinities between donor and acceptor are closely matched. Exploiting the chromophores as pre-calibrated electrostatic probes, the covalency of short hydrogen bonds as a non-electrostatic component was also revealed. No clear evidence was found for a possible contribution of unusually large polarizabilities of short hydrogen bonds due to proton delocalization; a theoretical framework for this interesting phenomenon is developed.<br></p>

scholarly journals Unusual Spectroscopic and Electric Field Sensitivity of a Chromophore with Short Hydrogen Bond: GFP and PYP as Model Systems

2020 ◽  
Author(s):  
Chi-Yun Lin ◽  
Steven Boxer
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Electric Field ◽  
External Electric Field ◽  
Heavy Atom ◽  
Model Systems ◽  
Donor And Acceptor ◽  
Short Hydrogen Bond ◽  
Structural Methods ◽  
Short Hydrogen Bonds

<p> Short hydrogen bonds, with heavy-atom distances less than 2.7 Å, are believed to exhibit proton delocalization and their possible role in catalysis has been widely debated. While spectroscopic and/or structural methods are usually employed to study the degree of proton delocalization, ambiguities still arise and no direct information on the corresponding potential energy surface is obtained. Here we apply an external electric field to perturb the short hydrogen bond(s) within a collection of green fluorescent protein S65T/H148D variants and photoactive yellow protein mutants, where the chromophore participates in the short hydrogen bond(s) and serves as an optical probe of the proton position. As the proton is charged, its position may shift in response to the external electric field, and the chromophore’s electronic absorption can thus reflect the ease of proton transfer. The results suggest that low-barrier hydrogen bonds are not present within these proteins even when proton affinities between donor and acceptor are closely matched. Exploiting the chromophores as pre-calibrated electrostatic probes, the covalency of short hydrogen bonds as a non-electrostatic component was also revealed. No clear evidence was found for a possible contribution of unusually large polarizabilities of short hydrogen bonds due to proton delocalization; a theoretical framework for this interesting phenomenon is developed.<br></p>

scholarly journals Machine learning models for hydrogen bond donor and acceptor strengths using large and diverse training data generated by first-principles interaction free energies

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Christoph A. Bauer ◽  
Gisbert Schneider ◽  
Andreas H. Göller
Keyword(s):  
Machine Learning ◽  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Training Data ◽  
Free Energies ◽  
Hydrogen Bond Donor ◽  
Chemical Application ◽  
Hydrogen Bond Acceptor ◽  
Donor And Acceptor ◽  
Target Values

Abstract We present machine learning (ML) models for hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD) strengths. Quantum chemical (QC) free energies in solution for 1:1 hydrogen-bonded complex formation to the reference molecules 4-fluorophenol and acetone serve as our target values. Our acceptor and donor databases are the largest on record with 4426 and 1036 data points, respectively. After scanning over radial atomic descriptors and ML methods, our final trained HBA and HBD ML models achieve RMSEs of 3.8 kJ mol−1 (acceptors), and 2.3 kJ mol−1 (donors) on experimental test sets, respectively. This performance is comparable with previous models that are trained on experimental hydrogen bonding free energies, indicating that molecular QC data can serve as substitute for experiment. The potential ramifications thereof could lead to a full replacement of wetlab chemistry for HBA/HBD strength determination by QC. As a possible chemical application of our ML models, we highlight our predicted HBA and HBD strengths as possible descriptors in two case studies on trends in intramolecular hydrogen bonding.

scholarly journals Electronic origin of the dependence of hydrogen bond strengths on nearest-neighbor and next-nearest-neighbor hydrogen bonds in polyhedral water clusters (H2O)n, n = 8, 20 and 24

2016 ◽  
Vol 18 (29) ◽  
pp. 19746-19756 ◽  
Author(s):  
Suehiro Iwata ◽  
Dai Akase ◽  
Misako Aida ◽  
Sotiris S. Xantheas
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Nearest Neighbor ◽  
Water Clusters ◽  
Hydrogen Donor ◽  
Donor And Acceptor ◽  
Bond Strengths

Comparison of the sum of the characteristic factors for some of the typical hydrogen donor and acceptor pairs with the CT term/kJ mol−1 (the upper value) and the O⋯O distance/in cubic (H2O)8.

scholarly journals Short hydrogen bonds in the catalytic mechanism of serine proteases

2008 ◽  
Vol 73 (4) ◽  
pp. 393-403 ◽  
Author(s):  
Vladimir Leskovac ◽  
Svetlana Trivic ◽  
Draginja Pericin ◽  
Mira Popovic ◽  
Julijan Kandrac
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Active Site ◽  
Serine Proteases ◽  
Active Sites ◽  
Catalytic Mechanism ◽  
Data Bank ◽  
Ground State Structure ◽  
Low Barrier Hydrogen Bonds ◽  
Short Hydrogen Bonds

The survey of crystallographic data from the Protein Data Bank for 37 structures of trypsin and other serine proteases at a resolution of 0.78-1.28 ? revealed the presence of hydrogen bonds in the active site of the enzymes, which are formed between the catalytic histidine and aspartate residues and are on average 2.7 ? long. This is the typical bond length for normal hydrogen bonds. The geometric properties of the hydrogen bonds in the active site indicate that the H atom is not centered between the heteroatoms of the catalytic histidine and aspartate residues in the active site. Taken together, these findings exclude the possibility that short "low-barrier" hydrogen bonds are formed in the ground state structure of the active sites examined in this work. Some time ago, it was suggested by Cleland that the "low-barrier hydrogen bond" hypothesis is operative in the catalytic mechanism of serine proteases, and requires the presence of short hydrogen bonds around 2.4 ? long in the active site, with the H atom centered between the catalytic heteroatoms. The conclusions drawn from this work do not exclude the validity of the "low-barrier hydrogen bond" hypothesis at all, but they merely do not support it in this particular case, with this particular class of enzymes.

Asymptotic Strength Limit of Hydrogen Bond Assemblies in Proteins at Vanishing Pulling Rates

2007 ◽  
Vol 1062 ◽  
Author(s):  
Sinan Keten ◽  
Markus J. Buehler
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Computational Studies ◽  
Entropic Elasticity ◽  
Strength Limit ◽  
Wide Range ◽  
Peptide Hydrogen ◽  
Polypeptide Chains ◽  
Limiting Value ◽  
Intrinsic Strength

ABSTRACTExperimental and computational studies on mechanical unfolding of proteins suggest that rupture forces approach a limiting value of a few hundred pN at vanishing pulling velocities. We develop a fracture mechanics based theoretical framework that considers the free energy competition between entropic elasticity of polypeptide chains and rupture of peptide hydrogen bonds, which we use here to provide an explanation for the intrinsic strength limit of proteins. Our analysis predicts that individual protein domains stabilized by hydrogen bonds can not exhibit rupture forces larger than approximately ≈200 pN, regardless of the presence of a large number of hydrogen bonds. This result explains a wide range of experimental and computational observations.

Sign in / Sign up

Export Citation Format

Share Document