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Tag Archives: molecular-dynamics
Project: Simulation of transmembrane transport

Project: Simulation of transmembrane transport

A central process in maintaining life is the transport of ions or small molecules such as nutrients across the cell membrane by secondary active transporter proteins. In this project you will use molecular dynamics (MD) computer simulations to study some of the fundamental principles by which transporters act as molecular machines that transduce energy through macromolecular conformational changes. In particular, you will attempt to solve a molecular puzzle : how can a large transported molecule fit through a transporter protein that according to experimental structural data appears too narrow?

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Project: Transport of divalent cations

Project: Transport of divalent cations

Divalent cations such as zinc or magnesium are essential for living organisms but the mechanisms by which they are transported into and out of the cell are not well understood at the molecular level. Classical molecular dynamics simulations of divalent ions are challenging because the high electric field strength near the ion leads to polarization effects that are not accurately accounted for in standard MD force fields. In this project you will explore alternative models for simulating divalent ions in order to find models that combine computational speed with sufficient accuracy to study transport of divalent ions with transporter proteins.

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Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

A new crystal structure of the Escherichia coli NhaA dimer reveals a previously unidentified salt bridge between two highly conserved residues at the putative binding site. The combination of structural data with molecular dynamics simulations yields new insights into the transport mechanism.

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Bedabrata Choudhury

Bedabrata Choudhury

In Fall 2014, Bedabrata started a rotation project on the molecular mechanism of temperature sensing. The goal of this project is to study the heat-sensitive TRPV1 ion channel with molecular dynamics (MD) simulations and identify regions or conformations of the protein that are sensitive to temperature changes. The work will be carried out in collaboration with the experimental lab of Dr van Horn in the Department of Chemistry and Biochemistry.

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Summer Book Club 2014: Molecular Simulations and Theory

Summer Book Club 2014: Molecular Simulations and Theory

This summer’s Lab Book Club is designed to provide a thorough review of fundamental concepts for understanding biomolecular simulation and, in particular,molecular dynamics simulations (MD). The material is primarily based on chapters from Statistical Mechanics: Theory and Molecular Simulation by Mark Tuckerman.

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Becksteinlab featured in A2C2 Quarterly

Becksteinlab featured in A2C2 Quarterly

The work in the lab was featured in the Winter 2014 edition of the A2C2 Quarterly newsletter.

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Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

We show that one of the best-studied secondary active transporters, the lactose permease LacY, goes through an occluded conformation during its transport cycle. We propose an atomically detailed model of the apo-occluded state. The simulations predict the formation of a transient salt bridge that has been hypothesized in the canonical model for transport of LacY. The simulations are validated by comparison to experimental EPR DEER data, using a new approach to simulate spin-label distance distributions through post-processing of molecular dynamics trajectories. We also define a set of order parameters that consistently classify all known MFS transporter structures as outward-open, occluded, or inward-open conformations.

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A two-domain elevator mechanism for sodium/proton antiport

A two-domain elevator mechanism for sodium/proton antiport

In a combined X-ray crystallography/biochemistry/molecular simulation study published in Nature we present the structure of the sodium/proton antiporter NapA in its outward facing conformation. Together with the inward facing conformation of the related transporter NhaA we can now understand the conformational changes required for the sodium/proton antiport mechanism.

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X-ray crystallography and Simulations

X-ray crystallography and Simulations

Structures of membrane proteins can be obtained by the experimental technique of X-ray crystallography. However, proteins are typically not crystallized in their native environment, the lipid membrane. Molecular dynamics simulations of the protein in the membrane provide a realistic model of the interactions between transporter and lipid bilayer.

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Tutorial: MDAnalysis

Tutorial: MDAnalysis

A short introductory tutorial on MDAnalysis

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Tutorial: Simulating AdK with Gromacs

Tutorial: Simulating AdK with Gromacs

A tutorial that teaches you to perform and analyze a molecular dynamics simulation of the the enzyme adenylate kinase (AdK) with the Gromacs simulation package.

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Molecular dynamics simulations

Molecular dynamics simulations

Molecular dynamics (MD) is a computational method to compute the trajectories of a large number of particles that interact with each other. Classical MD approximates interactions between atoms by classical forces but fully quantum mechanical MD has also been carried out. Experimental observables are calculated from trajectories using statistical mechanics.

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Long Liang

Long Liang

Long Liang majored in Biology in his undergraduate study, and shifted to Physics for his PhD study. He hopes to combine his background in Biology and Physics to understand life in terms of the more fundamental Physical laws. In his rotation project he worked on constructing a validated model of a human neurotransmitter transporter. Long is now part of the Complex Materials Group and works on his PhD under Professor Yang Jiao.

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Ian Welland

Ian Welland

Ian Welland graduated from ASU with a degree in physics in Summer 2015 and started in the Joint CMU-Pitt Ph.D. Program in Computational Biology in Fall 2015. During his time in Beckstein Lab, Ian worked on the problem of how to quantitatively describe and analyze the solvation of macromolecules

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MDAnalysis

MDAnalysis

MDAnalysis is an open source, versatile, object-oriented Python library for analyzing molecular dynamics trajectories. It makes it easy to access trajectory data from Python code by interfacing trajectory readers (and writers) with NumPy arrays and to select atoms via a expressive selection syntax. The CHARMM/NAMD, Amber, Gromacs trajectory formats are all supported as well as PDB, GRO, CRD, PQR, and a range of others.

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Simulations of membrane proteins

Simulations of membrane proteins

Many proteins in the living cell can be understood as molecular machines that use a source of energy to produce mechanical or chemical work. My lab’s primary interest is in those proteins located in the cell membrane that move nutrients, signalling molecules, or waste products into and out of the cell. We study their molecular mechanisms of action by detailed molecular dynamics simulations, which provide a “movie” of full atomic detail of a working protein.