Biomacromolecular systems

While organizing the symposium upon which this volume is based, the Macromolecular Science Division of the Chemical Institute of Canada attempted to include papers representing a wide range of applications for using Carbon-13 NMR to characterize polymers and to have both synthetic and biomacromolecular systems considered. 

The fifth section provides a brief description of multicanonical techniques and their use and applicability in MC simulations. We touch upon the benefits that MC techniques provide in sampling ensembles other than the canonical ensemble for biomacromolecular systems. 

Other advanced techniques and their applicability to biomacromolecular systems... 

Jorgensen, W.L., Tirado-Rives, J. Molecular modeling of organic and biomacromolecular systems using BOSS and MCPRO. J. Comput. Chem. 2005, 26, 1689-700. 

Water is an essential part in the biomacromolecular system, which is mainly responsible for the structure and functions of nucleic acids, proteins, and other constituents of cell [136-138]. Both proteins and DNA are generally hydrated. It is well known that the conformation of DNA is sensitive to hydration, and presence of salts and ligand molecules [112, 138]. The nucleic acids have three levels of water structure. About 12 water molecules per nucleotide are involved in the primary hydration shell [107, 112, 137, 138]. The water molecules present in the primary shell are impermeable to cations and do not form ice on freezing. The secondary level is permeable to cations and forms ice on freezing and third level is the completely disordered, so-called bulk water. Several theoretical studies have been carried out on the level of hydration on DNA bases, base pairs, base stacks, and double helical DNA [107, 121, 131, 139]. Both the experimental and molecular simulation studies have clearly brought out the importance of hydration in DNA and RNA structures [140-147]. 

Assfeld X, Ferre N, Rivail JL. The local self consistent field. Principles and applications to combined QM/MM computations on biomacromolecular systems. In Gao J, Thompson MA, eds. Combined Quantum Mechanical and Molecular Mechanical Methods. ACS Symposium Series 712. Washington, DC American Chemical Society, 1998 234-239. 

Cyclophilin A is a simple example pentamer and decamer share the same isometric form lattice. Moreover, the mutual orientation of the pentamers in the decameric configuration is fixed through a linear scaling transformation leaving the form lattice invariant. The geometry of the entire biomacromolecular system and of its components is expressible in term of the single parameter tq, which is the shortest distance of the monomeric chain from the fivefold axis. 

The molecular mechanical approach to simulating biomacromolecular structures by the use of potential energy functions has been discussed. These potential energy functions are an enthalpic contribution to the free energy, but the free energy contains entropic contribution. There are two forms of entropy in a biomacromolecular system namely the conformational entropy, which entails the inherent entropy of the biomacromolecular structure and the solvent entropy, which results from interactions between a biomacromolecule and solvent molecules. 

Complex supramolecular systems may also be studied by modem computational methods, which have become useful interpretative and predictive tools. Benedetta Menucci, Stefano Caprasecca and Giro Guido review environmental effects on properties and processes involving molecular probes in solution or in biomacromolecular systems. The capabilities of such techniques are demonstrated with a particular focus on simulations of spectroscopic properties, which allow for direct comparison between calculated and... 

Water molecules and H-bonds netwoik are essential stmctural components in various biomacromolecular systems such as nucleic acids complexes, membranes, fibrillar and globular proteins. The topology of water shell macromolecules strac-ture is important for understanding many of the processes occurring in a living cell... 

Quantum mechanics is essential for studying enzymatic processes [1-3]. Depending on the specific problem of interest, there are different requirements on the level of theory used and the scale of treatment involved. This ranges from the simplest cluster representation of the active site, modeled by the most accurate quantum chemical methods, to a hybrid description of the biomacromolecular catalyst by quantum mechanics and molecular mechanics (QM/MM) [1], to the full treatment of the entire enzyme-solvent system by a fully quantum-mechanical force field [4-8], In addition, the time-evolution of the macromolecular system can be modeled purely by classical mechanics in molecular dynamicssimulations, whereas the explicit incorporation... 

In biological systems, H-bond donors and acceptors are predominantly nitrogen and oxygen atoms. However, the n electrons of aromatic systems can also act as acceptors, and H-bonds involving sulfur groups or metallic cofactors are also known. The presence of individual H-bonds in biomacromolecular structures is usually derived from the spatial arrangement of the donor and acceptor groups once the structure of a molecule has been solved by diffractive or NMR techniques. More detailed information about H-bonds... 

We conclude by providing a few examples illustrating the peculiarities of sampling phase space via MC for nontrivial systems relevant to the biomacromolecular field. We provide an outlook regarding current challenges and the potential strategies that can be developed or adopted to overcome these challenges. 

Gordon VC (1992) Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic... 

The problem in trying to model the 3D structure of a biomacromolecular is formidable because of the large size and complexity of the system and therefore some simplifications and assumptions are required ... 

Most biomacromolecular interactions (bindings) involve the formation of some types of noncovalent bond and some specific region of the macromolecule called the binding site. Determinations of equilibrium binding processes are mostly indirect in that either i) the fraction of all of the ligand molecules (generally labeled molecules are used) in the system that are bound or ii) the fraction of binding sites that are occupied, is measured. 

When biomacromolecular embedding is considered, such as protein matrices and DNA structures, the discrete formulation is instead to be preferred in those cases a detailed and atomistic description of the macromo-lecular environment is necessary, in order to obtain accurate descriptions of the molecular process of interest. Moreover, for these systems, accurate force fields are generally available. Within this framework, the QM/MM approach is commonly used in combination with MD simulations to both achieve a proper statistical sampling and to account for the effects of fluctuations. Commonly the MD simulations are performed at a fiilly classical level (especially if the systems are large and the time-windows to be explored are long). In the 2010s, however, QM/MM-MD are also becoming feasible for small-medium QM systems for time windows of the order of tens to hundreds ofps. ... 

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