Molecular modeling for physical property prediction

Multiscale modeling is becoming the standard approach for process study in a broader framework that promotes computer aided integrated product and process design. In addition to usual purity requirements, end products must meet new constraints in terms of environmental impact, safety of goods and people, specific properties. This chapter adresses the use of molecular modeling tools for the prediction of physical property usefull for chemical engineering practice

Molecular modeling to study dendrimers for biomedical applications

© 2014 by the authors; licensee MDPI; Basel; Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). Date of Acceptance: 17/11/2014Molecular modeling techniques provide a powerful tool to study the properties of molecules and their interactions at the molecular level. The use of computational techniques to predict interaction patterns and molecular properties can inform the design of drug delivery systems and therapeutic agents. Dendrimers are hyperbranched macromolecular structures that comprise repetitive building blocks and have defined architecture and functionality. Their unique structural features can be exploited to design novel carriers for both therapeutic and diagnostic agents. Many studies have been performed to iteratively optimise the properties of dendrimers in solution as well as their interaction with drugs, nucleic acids, proteins and lipid membranes. Key features including dendrimer size and surface have been revealed that can be modified to increase their performance as drug carriers. Computational studies have supported experimental work by providing valuable insights about dendrimer structure and possible molecular interactions at the molecular level. The progress in computational simulation techniques and models provides a basis to improve our ability to better predict and understand the biological activities and interactions of dendrimers. This review will focus on the use of molecular modeling tools for the study and design of dendrimers, with particular emphasis on the efforts that have been made to improve the efficacy of this class of molecules in biomedical applications.Peer reviewedFinal Published versio

MOLECULAR MODELING OF HYALURONIC ACID CONTANING CISPLATIN-LOADED POLYLAGTIC-CO-GLYCOLIC ACID BIOCONJUGATES FOR TARGETED DELIVERY TO CANCER CELLS

This project will present the molecular modeling of hyaluronic acid (HA), cisplatin, polylactic-co-glycolic acid (PLGA) and PEG-his amine as uni-molecular modeling and also conjugated forms of multi-molecular modeling for targeted delivery to cancer cells in 3D format by using Discovery Studios 2.5 software from Accelrys Inc. USA. Colorectal cancer cell will be the case study for targeted drug delivery. The methodologies to be used include molecular modeling design are molecular modeling, model development of cisplatin, PLGA, and HA. The simulation studies on drug delivery to colorectal cancer cells of the bioconjugated forms of the compounds will also be carried on

The structure of the agrochemical fungicidal 4-Chloro-3-(3,5-dichloropheny)-1H-pyrazole, RPA 406194 and related compounds

The difficulties to obtain convenient monocrystals of the important fungicide RPA 406194 have been overcome by a combination of solid state 13C NMR, X-ray powder diffraction and molecular modeling. The compound, a 3-aryl tautomer, crystallizes forming infinite chains of molecules bonded by N–H· · ·N hydrogen bonds, leading to needle-shaped crystals. The tautomerism (equilibrium constant and energy barrier) of this compound in solution has been studied

Theoretical description of a DNA-linked nanoparticle self-assembly

Nanoparticles tethered with DNA strands are promising building blocks for bottom-up nanotechnology, and a theoretical understanding is important for future development. Here we build on approaches developed in polymer physics to provide theoretical descriptions for the equilibrium clustering and dynamics, as well as the self-assembly kinetics of DNA-linked nanoparticles. Striking agreement is observed between the theory and molecular modeling of DNA tethered nanoparticles.Comment: Accepted for publication in Physical Review Letter

Computational structure‐based drug design: Predicting target flexibility

The role of molecular modeling in drug design has experienced a significant revamp in the last decade. The increase in computational resources and molecular models, along with software developments, is finally introducing a competitive advantage in early phases of drug discovery. Medium and small companies with strong focus on computational chemistry are being created, some of them having introduced important leads in drug design pipelines. An important source for this success is the extraordinary development of faster and more efficient techniques for describing flexibility in three‐dimensional structural molecular modeling. At different levels, from docking techniques to atomistic molecular dynamics, conformational sampling between receptor and drug results in improved predictions, such as screening enrichment, discovery of transient cavities, etc. In this review article we perform an extensive analysis of these modeling techniques, dividing them into high and low throughput, and emphasizing in their application to drug design studies. We finalize the review with a section describing our Monte Carlo method, PELE, recently highlighted as an outstanding advance in an international blind competition and industrial benchmarks.We acknowledge the BSC-CRG-IRB Joint Research Program in Computational Biology. This work was supported by a grant from the Spanish Government CTQ2016-79138-R.J.I. acknowledges support from SVP-2014-068797, awarded by the Spanish Government.Peer ReviewedPostprint (author's final draft

The LBFGS Quasi-Newtonian Method for Molecular Modeling Prion AGAAAAGA Amyloid Fibrils

Experimental X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, dual polarization interferometry, etc are indeed very powerful tools to determine the 3-Dimensional structure of a protein (including the membrane protein); theoretical mathematical and physical computational approaches can also allow us to obtain a description of the protein 3D structure at a submicroscopic level for some unstable, noncrystalline and insoluble proteins. X-ray crystallography finds the X-ray final structure of a protein, which usually need refinements using theoretical protocols in order to produce a better structure. This means theoretical methods are also important in determinations of protein structures. Optimization is always needed in the computer-aided drug design, structure-based drug design, molecular dynamics, and quantum and molecular mechanics. This paper introduces some optimization algorithms used in these research fields and presents a new theoretical computational method - an improved LBFGS Quasi-Newtonian mathematical optimization method - to produce 3D structures of Prion AGAAAAGA amyloid fibrils (which are unstable, noncrystalline and insoluble), from the potential energy minimization point of view. Because the NMR or X-ray structure of the hydrophobic region AGAAAAGA of prion proteins has not yet been determined, the model constructed by this paper can be used as a reference for experimental studies on this region, and may be useful in furthering the goals of medicinal chemistry in this field