Advertisement

Topics

Haptic-assisted interactive molecular docking incorporating receptor flexibility.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "Haptic-assisted interactive molecular docking incorporating receptor flexibility."

Haptic-assisted interactive docking tools immerse the user in an environment where intuition and knowledge can be used to help guide the docking process. Here we present such a tool where the user "holds" a rigid ligand via a haptic device through which they feel interaction forces with a flexible receptor biomolecule. To ensure forces transmitted through the haptic device are smooth and stable, they must be updated at a rate greater than 500 Hz. Due to this time constraint, the majority of haptic docking tools do not attempt to model the conformational changes that would occur when molecules interact during binding. Our haptic-assisted docking tool, "Haptimol Flexidock", models a receptor's conformational response to forces of interaction with a ligand whilst maintaining the required haptic refresh rate. In order to model receptor flexibility we use the method of linear response for which we determine the variance-covariance matrix of atomic fluctuations from the trajectory of an explicit-solvent Molecular Dynamics simulation of the ligand-free receptor molecule. Key to satisfying the time constraint is an eigenvector decomposition of the variance-covariance matrix which enables a good approximation to the conformational response of the receptor to be calculated rapidly. This exploits a feature of protein dynamics whereby most fluctuation occurs within a relatively small subspace. The method is demonstrated on Glutamine Binding Protein in interaction with glutamine, and Maltose Binding Protein in interaction with maltose. For both proteins, the movement that occurs when the ligand is docked near to its binding site matches the experimentally determined movement well. It is thought that this tool will be particularly useful for structure-based drug design.

Affiliation

Journal Details

This article was published in the following journal.

Name: Journal of chemical information and modeling
ISSN: 1549-960X
Pages:

Links

DeepDyve research library

PubMed Articles [16344 Associated PubMed Articles listed on BioPortfolio]

CABS-dock standalone: a toolbox for flexible protein-peptide docking.

CABS-dock standalone is a multiplatform Python package for protein-peptide docking with backbone flexibility. The main feature of the CABS-dock method is its ability to simulate significant backbone f...

Reliability of docking-based virtual screening for GPCR ligands with homology modeled structures: a case study of angiotensin II type I receptor.

The number of solved G protein-coupled receptor (GPCR) crystal structures has expanded rapidly, but most GPCR structures remain unsolved. Therefore, computational techniques, such as homology modeling...

Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y receptor antagonists.

A novel series of 2-(phenoxyaryl)-3-urea derivatives were designed, synthesized, and biologically evaluated for their anti-thrombotic activity. Most of compounds exhibited good inhibition against P2Y ...

Haptic feedback in the da Vinci Research Kit (dVRK): a user study based on grasping, palpation and incision tasks.

It was suggested that the lack of haptic feedback, formerly considered a limitation for the da Vinci robotic system, does not affect robotic surgeons because of training and compensation based on visu...

Haptic perception is altered in children with developmental coordination disorder.

Developmental coordination disorder (DCD) is a neurodevelopmental disorder affecting the motor system, but it may also present with signs of somatosensory dysfunction. This study examined whether hapt...

Clinical Trials [5812 Associated Clinical Trials listed on BioPortfolio]

A Novel Walking Cane With Haptic Biofeedback Reduces Degenerative Loading in the Arthritic Knee

The most commonly prescribed mobility aid, the walking cane, is often underloaded and therefore fails to reduce knee joint loading and provide symptomatic relief for those with knee osteoa...

A Pilot Study of Robot-assisted Therapy for Post-stroke Forearm and Wrist Rehabilitation Training

A pilot study to assess the effectiveness of CR2-Haptic and determine the feasibility of including robotic therapy into the daily rehabilitation program.

Comparison of Haptic Orientation in Negative Dysphotopsia

Previous studies attempted to understand the dysphotopsia phenomenon by examining IOL type, anterior capsule depth, iris-to-lens depth, lens refractive material, clear cornea incision woun...

Verticality Perception Assessed by the Haptic Vertical

The investigators previously shown that a rotating optokinetic stimulus results in shifts of the subjective visual vertical in healthy human subjects. However, the origin of these shifts i...

Breast Cancer Proteomics and Molecular Heterogeneity

Primary objective: The primary objective is to define the proteomic and molecular characteristics of primary and recurrent/ metastatic breast tumours with special focus on the expression ...

Medical and Biotech [MESH] Definitions

A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.

Use of an interactive computer system designed to assist the physician or other health professional in choosing between certain relationships or variables for the purpose of making a diagnostic or therapeutic decision.

The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.

Mechanical ventilation delivered to match the patient's efforts in breathing as detected by the interactive ventilation device.

Therapy assisted by the use of a horse and/or its movement, including equine-assisted psychotherapy, horseback riding, and hippotherapy.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Article