scholarly journals Calculation of substrate binding affinities for a bacterial GH78 rhamnosidase through molecular dynamics simulations

2013 ◽  
Vol 92 ◽  
pp. 34-43 ◽  
Author(s):  
Melanie Grandits ◽  
Herbert Michlmayr ◽  
Christoph Sygmund ◽  
Chris Oostenbrink
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Substrate Binding ◽  
Binding Affinities ◽  
Dynamics Simulations

A molecular dynamics study of the complete binding process of meropenem to New Delhi metallo-β-lactamase 1

2018 ◽  
Vol 20 (9) ◽  
pp. 6409-6420 ◽  
Author(s):  
Juan Duan ◽  
Chuncai Hu ◽  
Jiafan Guo ◽  
Lianxian Guo ◽  
Jia Sun ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Substrate Binding ◽  
New Delhi ◽  
Binding Process ◽  
Dynamics Simulations

We have investigated the substrate-binding pathways of NDM-1 via unbiased molecular dynamics simulations and metadynamics.

scholarly journals The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor

2020 ◽  
Author(s):  
Esther S. Brielle ◽  
Dina Schneidman-Duhovny ◽  
Michal Linial
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Cell Receptor ◽  
Host Recognition ◽  
Interface Residue ◽  
Binding Affinities ◽  
Temporal Dimension ◽  
Binding Interface ◽  
Residue Contacts ◽  
Dynamics Simulations

AbstractThe COVID-19 disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies.One Sentence SummaryMolecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor.

scholarly journals Interrogating RNA-small molecule interactions with structure probing and AI augmented-molecular simulations

2021 ◽  
Author(s):  
Yihang Wang ◽  
Shaifaly Parmar ◽  
John S. Schneekloth ◽  
Pratyush Tiwary
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Ligand Recognition ◽  
Binding Affinities ◽  
Structure Probing ◽  
Mutational Profiling ◽  
In Vitro Measurements ◽  
Molecule Interactions ◽  
Dynamics Simulations

While there is increasing interest in the study of RNA as a therapeutic target, efforts to understand RNA-ligand recognition at the molecular level lag far behind our understanding of protein-ligand recognition. This problem is complicated due to the more than ten orders of magnitude in timescales involved in RNA dynamics and ligand binding events, making it not straightforward to design experiments or simulations. Here we make use of artificial intelligence (AI)-augmented molecular dynamics simulations to directly observe ligand dissociation for cognate and synthetic ligands from a riboswitch system. The site-specific flexibility profiles from our simulations are in excellent agreement with in vitro measurements of flexibility using Selective 2' Hydroxyl Acylation analyzed by Primer Extension and Mutational Profiling (SHAPE-MaP). Our simulations reproduce known binding affinity profiles for the cognate and synthetic ligands, and pinpoint how both ligands make use of different aspects of riboswitch flexibility. On the basis of our dissociation trajectories, we also make and validate predictions of pairs of mutations for both the ligand systems that would show differing binding affinities. These mutations are distal to the binding site and could not have been predicted solely on the basis of structure. The methodology demonstrated here shows how molecular dynamics simulations with all-atom force-fields have now come of age in making predictions that complement existing experimental techniques and illuminate aspects of systems otherwise not trivial to understand.

scholarly journals Substrate Binding at the Qo-Site of the Bacterial Cytochrome bc1 Complex Predicted by Atomistic Molecular Dynamics Simulations

2013 ◽  
Vol 104 (2) ◽  
pp. 490a
Author(s):  
Pekka A. Postila ◽  
Karol Kaszuba ◽  
Marcin Sarewicz ◽  
Artur Osyczka ◽  
Ilpo Vattulainen ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Substrate Binding ◽  
Cytochrome Bc1 ◽  
Bc1 Complex ◽  
Cytochrome Bc1 Complex ◽  
Qo Site ◽  
Dynamics Simulations

Molecular Simulations to Rationalize Humanized Ab2/3H6 Activity

2011 ◽  
Vol 64 (7) ◽  
pp. 900 ◽  
Author(s):  
Anita de Ruiter ◽  
Alexander Mader ◽  
Renate Kunert ◽  
Chris Oostenbrink
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Heavy Chain ◽  
Free Energy Calculations ◽  
Binding Affinities ◽  
Dynamics Simulations ◽  
Idiotypic Antibody ◽  
Mouse Antibody ◽  
Hiv 1

The murine anti-idiotypic antibody 3H6 (Ab2/3H6) is directed against the human 2F5 antibody, which is capable of neutralizing HIV-1. Recently, four humanized Ab2/3H6 models have been developed in order to reduce the risk of human anti-mouse antibody (HAMA) responses in case of administration to humans. In this study, molecular dynamics simulations were performed on these models as well as on the murine Ab2/3H6 in solution and bound to 2F5, in order to rationalize the differences in binding affinities of the models towards 2F5. Analysis of these simulations suggested that the orientation and dynamics of the residues TYR54 and TYR103 of the heavy chain of Ab2/3H6 play an important role in these differences. Subsequently, the contribution of these residues to the binding affinity was quantified by applying free energy calculations.

scholarly journals ROLE OF SUBSTRATE BINDING ON THE PROTEIN DYNAMICS OF AN ENDOGLUCANASE FROM FUSARIUM OXYSPORUM AT DIFFERENT TEMPERATURES

2018 ◽  
Vol 19 (1) ◽  
pp. 307-314
Author(s):  
ABDUL AZIZ AHMAD ◽  
Hamzah Mohd. Salleh ◽  
IBRAHIM ALI NOORBATCHA
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Fusarium Oxysporum ◽  
Protein Dynamics ◽  
Substrate Binding ◽  
Solvent Accessible Surface Area ◽  
Enzyme Complex ◽  
Different Temperatures ◽  
Endoglucanase I ◽  
Dynamics Simulations

: Thermostability is an important requirement for protein function, and one goal of protein engineering is improvement of activity of the enzymes at higher temperatures, particularly for industrial applications. Computational approaches to investigate factors influencing thermostability of proteins are becoming researchers’ choice. This study investigates the influence of substrate binding on the protein dynamics by comparing the molecular dynamics simulations of substrate-enzyme complex against un-bound enzyme, using endoglucanase I from Fusarium oxysporum. Endoglucanase-substrate complex was prepared by docking and molecular dynamics simulations were carried out at three different temperatures, 313 K, 333 K and 353 K. Our finding shows that the secondary structures for substrate-enzyme complex show more fluctuations relative to un-complexed structure. The same trend was observed for solvent accessible surface area and radius of gyration. At the highest temperature studied (353 K), the substrate-enzyme complex form showed the highest fluctuations. The fluctuations around the active site regions reach a minimum at the optimum temperature, compared to the other structural regions and other temperatures. ABSTRAK: Kestabilan (ketahanan) terhadap haba merupakan keperluan yang penting untuk fungsi protin, salah satu matlamat kejuruteraan protin adalah penambahbaikan aktiviti enzim pada suhu yang tinggi khususnya untuk aplikasi industri. Kini para penyelidik memilih kaedah komputasi, bagi mengkaji faktor yang mempengaruhi kestabilan terhadap haba. Kajian ini menyelidik pengaruh ikatan substrat pada protin dengan membandingkan simulasi molekular dinamik diantara substrat-enzim kompleks dan enzim sahaja, menggunakan endoglucanase I dari Fusarium oxysporum. Kompleks endoglucanase-substrat disediakan melalui kaedah docking dan simulasi molekular dinamik dilakukan pada suhu 313 K, 333 K dan 353 K. Kajian kami menunjukkan struktur sekunder bagi substrat-enzim kompleks kurang stabil berbanding enzim sahaja. Pola yang sama bagi luas permukaan boleh dicapai pelarut (SASA) dan jejari gyrasi. Pada suhu tertinggi dikaji (353 K), substrat-enzim kompleks paling tidak stabil. Pada suhu optimum, kadar ubah-ubah sekitar amino asid aktif adalah minimum berbanding struktur dan suhu lain.  

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