Henri Temianka Correspondence; (laughton)

https://digitalcommons.chapman.edu/temianka_correspondence/2278/thumbnail.jp

Henri Temianka Correspondence; (laughton)

https://digitalcommons.chapman.edu/temianka_correspondence/2280/thumbnail.jp

Tios: The Internet of Simulations. Turning Molecular Dynamics into a Data Streaming Web Application

The configuration of most current academic high-performance computing (HPC) resources tends to enforce ways of working with, and thinking about, molecular dynamics (MD) simulations that are not always optimal. For example, when the aim of the simulation(s) is to produce a representative sample of a Boltzmann weighted ensemble, the ideal scenario would be to be able to do just that—i.e. to tap into a running simulation of indefinite length, collect data from it in real time, and only terminate the simulation once the quality of a sample was assured. Current approaches, based on batch jobs of proscribed maximum length, and a postprocessing style of data analysis, inhibit this. In the spirit of the Internet of Things, we have developed Tios, a Python application that turns MD simulations into remotely discoverable and accessible streaming web applications to which researchers can connect and download data as they please. Tios is freely available, works with standard MD codes, and requires no modifications to them. In this paper we outline how Tios works and present a number of test cases that demonstrate its capabilities

Determination of the Rate of Drying of Abattoir Cow Paunch Content (CPC) as a Function of Relative Humidity, Depth and Age

Agricultural Engineerin

Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations

We have investigated the effects of duplex length, sequence, salt concentration and superhelical density on the conformation of DNA nanocircles containing up to 178 base pairs using atomistic molecular dynamics simulation. These calculations reveal that the partitioning of twist and writhe is governed by a delicate balance of competing energetic terms. We have identified conditions which favour circular, positively or negatively writhed and denatured DNA conformations. Our simulations show that AT-rich DNA is more prone to denaturation when subjected to torsional stress than the corresponding GC containing circles. In contrast to the behaviour expected for a simple elastic rod, there is a distinct asymmetry in the behaviour of over and under-wound DNA nanocircles. The most biologically relevant negatively writhed state is more elusive than the corresponding positively writhed conformation, and is only observed for larger circles under conditions of high electrostatic screening. The simulation results have been summarised by plotting a phase diagram describing the various conformational states of nanocircles over the range of circle sizes and experimental conditions explored during the study. The changes in DNA structure that accompany supercoiling suggest a number of mechanisms whereby changes in DNA topology in vivo might be used to influence gene expression

Exploring the Counterion Atmosphere around DNA: What Can Be Learned from Molecular Dynamics Simulations?

AbstractThe counterion distribution around a DNA dodecamer (5′-CGCGAATTCGCG-3′) is analyzed using both standard and novel techniques based on state of the art molecular dynamics simulations. Specifically, we have explored the population of Na+ in the minor groove of DNA duplex, and whether or not a string of Na+ can replace the spine of hydration in the narrow AATT minor groove. The results suggest that the insertion of Na+ in the minor groove is a very rare event, but that when once the ion finds specific sites deep inside the groove it can reside there for very long periods of time. According to our simulation the presence of Na+ inside the groove does not have a dramatic influence in the structure or dynamics of the duplex DNA. The ability of current MD simulations to obtain equilibrated pictures of the counterion atmosphere around DNA is critically discussed

Multiscale modelling of drug-polymer nanoparticle assembly identifies parameters influencing drug encapsulation efficiency

Using a multiscale (dual resolution) approach combining an atomistic (GROMOS96) and coarse-grain (MARTINI) force field, we have been able to simulate the process of drug-polymer nanoparticle assembly by nanoprecipitation from mixed solvents. Here we present the development and application of this method to the interaction of three poly(glycerol adipate) polymer variants with the anti-cancer drug dexamethasone phosphate. Differences in encapsulation efficiency and drug loading between the polymers are in agreement with the experimental trend. Reference atomistic simulations at key points along the predicted aggregation pathway support the accuracy of the much more compute-efficient multiscale methodology

Ligand-induced conformational selection predicts the selectivity of cysteine protease inhibitors

Cruzain, a cysteine protease of Trypanosoma cruzi, is a validated target for the treatment of Chagas disease. Due to its high similarity in three-dimensional structure with human cathepsins and their sequence identity above 70% in the active site regions, identifying potent but selective cruzain inhibitors with low side effects on the host organism represents a significant challenge. Here a panel of nitrile ligands with varying potencies against cathepsin K, cathepsin L and cruzain, are studied by molecular dynamics simulations as both non-covalent and covalent complexes. Principal component analysis (PCA), identifies and quantifies patterns of ligand-induced conformational selection that enable the construction of a decision tree which can predict with high confidence a low-nanomolar inhibitor of each of three proteins, and determine the selectivity for one against others

BioSimSpace: An interoperable Python framework for biomolecular simulation

BioSimSpace is an interoperable Python framework for biomolecular simulation. With it you can: Write robust and portable biomolecular workflow components that work on different hardware, with different software packages, and that can be run in different ways, e.g. command-line, Jupyter. Interact with molecular-simulation processes in real time