ACM Computing Reviews for my Springer BOOKS

Molecular structures and structural dynamics of prion proteins and prions : mechanism underlying the resistance to prion diseases

Zhang J., Springer International Publishing, New York, NY, 2015. 355 pp. Type: Book (978-9-401773-17-1). Date Reviewed: Sep 9 2016. Computing Review of ACM - Reviewer: Anthony J. Duben. Review #: CR144750 (1612-0878).

Unlike bacteria and viruses, which are based on DNA and RNA, prions are unique as disease-causing agents since they are misfolded proteins. Prions propagate by deforming harmless, correctly folded proteins into copies of themselves. The misfolding is irreversible. Prions attack the nervous system of the organism, causing an incurable, fatal deterioration of the brain and nervous system until death occurs. Some examples of these diseases are mad cow disease in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans.

Not every species is affected by prion disease. Rabbits, water buffalo, horses, and dogs are resistant to prion diseases. The research question arises: What is different about the protein in a resistant species (especially the rabbit, which seems to be the most resistant) that allows it to retain its folding? This is the research question addressed in this book. The original research reported in this volume is based on molecular modeling since the usual experimental tools for structure elucidation at the molecular level, X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, are often unsuitable for studying proteins. The computational simulation of the interactions within and among proteins is used to interpret the stability of conformations as they fold and as they pack in a cluster of proteins.

After an introductory chapter in which the author describes the proteins in question and a quick overview of molecular dynamics and molecular mechanics, this book is organized into two parts. The first part is a set of nine chapters in which the author presents primarily the results of his research using the molecular dynamics of segments of the proteins of comparable species in order to explain why rabbits resist prion infection while other susceptible species do not. The second part consists of eight chapters emphasizing the optimization methods used in molecular modeling and molecular dynamics.

In the first part, the molecular dynamics simulations are performed at different computational temperatures and at low, high, and neutral pH levels. Segments of the proteins are selected for detailed analysis. The simulations suggest strongly that the prion-resistant species have stronger intra- and inter-chain interactions in specific segments of the protein chain that stabilize their geometries.

The second part discusses the optimization algorithms used: steepest descent, simulated annealing, genetic algorithm, evolutionary optimization, and combinations of these algorithms. The computational goal is identifying the low-energy conformations and their relative stability with respect to each other, especially the differences between the protein and the prion.

There is much that is very good about this book: the reporting of research results comparing different segments of different species’ proteins, the critical reviews of the existing literature, the extensive bibliography (over 700 publications), and the discussion of the optimization techniques. On the other hand, there are shortcomings: the repetitiveness in introducing each chapter by describing the research problem as if it were brand new; the colored figures that are supposed to show changes in conformation are so small that the scales on the axes cannot be read and they are accompanied by figure descriptions that discuss letter codes, not colors; a section discussing important results presented in a figure in a reference, without reprinting the figure in the book; and the poor copy editing that allowed errors in English grammar and scientific descriptions. It seems that the book was created by taking individual papers and assembling them in sequence with little attention to concision and cohesiveness. Nonetheless, if one can endure and overlook the many flaws in presentation, there is a wealth of information and insight in the results presented and in the methods employed. The research is important. The methods used are innovative. Studying this book is worth the effort.

Optimization-based molecular dynamics studies of SARS-CoV-2 molecular structures: research on COVID- 19

Zhang J., Springer International Publishing,Cham, Switzerland,2023. 953 pp.Type:Book. Date Reviewed: 05/26/25. Computing Review of ACM - Reviewer: Anthony J. Duben. Review #: CR147951.

The urgent need to develop COVID-19 vaccines, medications, and treatments led to an unprecedented level of activity in research labs. Computational chemistry was an integral part of the research efforts because it could reveal details of the interactions between components of the COVID-19 virus, receptor sites on the cell being attacked, and potential drugs. The principal computational technique used was molecular dynamics (MD), which can reveal changes in the 3D molecular structures in both the attacking and attacked molecules as they interact.

This 900-plus-page book is a compilation of the results of computations performed using components of the COVID-19 virus (including the spike proteins--both with and without glycosylation, membrane glycoproteins, envelope glycoproteins, and their variants in the principal mutations), human proteins and the ACE2 enzyme (the target of COVID-19), the related coronaviruses SARS and MERS, human immunodeficiency virus (HIV) inhibitors, scores of potential drugs, and vaccine components. This list is not exhaustive.

The book is presented in 28 chapters, plus a short appendix on MD optimization algorithms, references, and an index. The chapters follow a similar format. Each chapter begins with a brief introduction in which the central substances are presented, followed by another short section on the materials (for example, the specific portions of the interacting molecules) and the methods (the scope of the MD calculations, such as the software package used, force field parameter sets, solvent composition, and time period covered in the calculation). The bulk of the chapter is the results and discussion section, which contains many lengthy tables of likely close contacts between components of each interacting substance (for example, amino acids in each of the two proteins). Since the amino acids are numbered in the standard structural databases, it is possible to work backwards to reveal the structural environments of these contacts. This section also includes some graphics displaying the progress of the MD calculations and some molecular diagrams. Unfortunately, these graphics have been too reduced in size to easily perceive what they are supposed to illustrate. There is a short conclusion. Several of these chapters are followed by a lengthy supplemental section with many more tables of data results selected from the MD trajectories plus additional small graphics. The number and length of the tables is overwhelming.

There is little critical discussion of the MD calculations themselves or their optimization. However, data taken from the literature and archives is analyzed and could be used comparatively by other researchers investigating these COVID-19 systems. The structure of the book and data presented restrict the book’s primary use as a reference resource.

Introduction to the Computing Reviews of ACM:

https://en.wikipedia.org/wiki/ACM_Computing_Reviews

ACM Computing Reviews (CR) is a scientific journal that reviews literature in the field of computer science. It is published by the Association for Computing Machinery and the editor-in-chief is Carol Hutchins (New York University).[1]