Search results for "molecular dynamics"

Physical Origin and Biological Significance of Solvent Induced Forces

1994

The notion of solvent-induced forces (SIFs), as distinct from solute-solute forces acting through the solvent, is illustrated in terms of: i) the microscopic space-and time-resolved view provided by Molecular Dynamics Simulations; ii) the standard statistical-mechanical formulation, and iii) the inherent structures of water. It is shown that the origin of SIFs is in the non-additivity of the effects of solute-perturbation on the H-bond network in the solvent. This nonadditivity does not require non-additivity of water-water and solute-water interaction potentials. Two experimental studies, illustrating different aspects of SIFs are discussed in detail. One is the case of Human Adult Hemoglo…

Correction to "Probing the Accuracy of Explicit Solvent Constant pH Molecular Dynamics Simulations for Peptides".

2020

Interaction of explicit solvent with hydrophobic/philic/charged residues of a protein: Residue character vs. conformational context

1998

Molecular dynamics simulations of model solutes in explicit molecular water have recently elicited novel aspects of the strong nonpair additivity of the potential of mean force (PMF) and related solvent-induced forces (SIFs) and hydration. Here we present the results of the same type of work on SIFs acting on bovine pancreatic trypsin inhibitor (BPTI) at single residue/sidechain resolution. In this system, nonpair additivity and the consequent dependence of SIFs on the protein conformational context are sufficiently strong to overturn SIFs on some individual residues, relative to expectations based on their individual characters. This finding calls for a revisitation and offers a richer and…

Molecular aggregates of quinuclidine and chlorophyll a

1991

A slightly polar molecule quinuclidine seems to form weakly bound aggregates in concentrated water solutions. Molecular dynamics simulation of a 6 mol water solution indicates clustering of quinuclidine molecules into an almost spherical structure with polar ends of the molecules pointing towards the solvent. Experimental evidence of aggregation was obtained by observing a small but obvious red shift of the o'' a absorption and a dramatic shortening of the fluorescence lifetime of the c n transition of concentrated solutions. The observed self-quenching is interpreted in terms of Frster model for energy transfer in the cluster. It is estimated that excitation may migrate on the cluster surf…

Bill2d - a software package for classical two-dimensional Hamiltonian systems

2015

Abstract We present Bill2d , a modern and efficient C++ package for classical simulations of two-dimensional Hamiltonian systems. Bill2d can be used for various billiard and diffusion problems with one or more charged particles with interactions, different external potentials, an external magnetic field, periodic and open boundaries, etc. The software package can also calculate many key quantities in complex systems such as Poincare sections, survival probabilities, and diffusion coefficients. While aiming at a large class of applicable systems, the code also strives for ease-of-use, efficiency, and modularity for the implementation of additional features. The package comes along with a use…

Polynucleotide differentiation using hybrid solid-state nanopore functionalizing with α-hemolysin

2019

We report results from full atomistic molecular dynamics simulations on the properties of biomimetic nanopores. This latter result was obtained through the direct insertion of an α-hemolysin protein inside a hydrophobic solid-state nanopore. Upon translocation of different DNA strands, we demonstrate here that the theoretical system presents the same discrimination properties as the experimental one obtained previously. This opens an interesting way to promote the stability of a specific protein inside a solid nanopore to develop further biomimetic applications for DNA or protein sequencing.

Molecular mechanism of T-cell protein tyrosine phosphatase (TCPTP) activation by mitoxantrone.

2013

T-cell protein tyrosine phosphatase (TCPTP) is a ubiquitously expressed non-receptor protein tyrosine phosphatase. It is involved in the negative regulation of many cellular signaling pathways. Thus, activation of TCPTP could have important therapeutic applications in diseases such as cancer and inflammation. We have previously shown that the α-cytoplasmic tail of integrin α1β1 directly binds and activates TCPTP. In addition, we have identified in a large-scale high-throughput screen six small molecules that activate TCPTP. These small molecule activators include mitoxantrone and spermidine. In this study, we have investigated the molecular mechanism behind agonist-induced TCPTP activation.…

Self-assembly of a bioelastomeric structure: solution dynamics and the spinodal and coacervation lines.

1990

The stability, metastability, and instability regions of aqueous solutions of a representative synthetic bioelastomeric polymer, poly (Val-Pro-Gly-Val-Gly), were determined by a combined use of elastic and quasi-elastic light scattering experiments. The approach followed here offers the attractive advantage of singling out the relevant contributions to the total scattering even in the presence of traces of noninteracting larger sized impurities. Conclusions so reached were checked by means of independent experiments. The present results provide descriptions of the very early events in the physics of bioelastogenesis in terms of general polymer science and phase transitions, and in terms of …

Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.

2021

The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…

Low density lipoproteins and human serum albumin as the carriers of squalenoylated drugs: insights from molecular simulations

2018

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulate inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the bloodstream. Interaction of gemcitabine-squalene with human serum albumin (HSA) was also studied by ensemble of dockin…