Usage Of Computational Tools Research Articles

Properties of monomeric Aβ42 probed by different sampling methods and force fields: Role of energy components

Aggregation of intrinsically disordered proteins (IDPs), such as amyloid beta peptide, can cause serious health problems, associated with disorders including Alzheimer disease. Due to the lack of a stable structure and transient nature, such proteins and peptides are often very difficult or even impossible to study using experimental approaches. Therefore, usage of computational tools can provide valuable insight into their dynamics, structural changes, and mechanism of aggregation. Because current force fields were designed to work well for standard proteins with a well-defined native structure and high conformational stability, we examined three force fields most frequently used for studies of proteins, and two variants modified for better performance for IDPs on an example of monomeric amyloid beta 42 (Aβ42) with two sampling approaches: single 10 µs long conventional molecular dynamics (CMD) trajectories and 48-replica runs using the replica exchange MD (REMD). We found that newer force fields (Amber FF14SB and CHARMM36m) provided better results than their older versions (Amber FF99SB and CHARMM36), while the specially modified version for the IDPs (FF14SB_IDPs) yielded similar results to its parent, improving sampling using CMD simulations, hence allowing to achieve a similar level of accuracy at significantly lower computational costs. With sufficient sampling, the newer force fields provided good agreement with the available experimental data. We also analyzed the physical basis of different behaviors of force fields and sampling methods, concluding that in CHARMM interactions with water play a much more important role than in Amber force fields. This explains why, in CHARMM force fields, the monomeric Aβ42 is less stable and more hydrophilic, having a greater solvent accessible surface area.

Usability of contemporary tools for the computational design of architectural objects: Review, features evaluation and reflection

This article is an overview focused on functionality and usability of selected contemporary approaches for the computational floor plan generation of architectural objects. This article describes current solutions for generative architectural design and focuses on their usability from the point of view of architectural design practice. Recent research papers and prototypes, as well as the most important tools (selected computer-aided design and BIM software) for generative design from the architectural perspective, are described. The functionalities and level of usability of present-day software and prototypes are described. In addition, the descriptive review of the research prototypes architectural design outcomes is present. Furthermore, the survey among active architects regarding the usage of computational tools in the professional practice and possible guidelines for the development of such tools are present. This article summarises with the conclusion about the current state of generative floor plan design tools, the lack of fully functional and developed commercial tools of this type on the market and future directions for the development of generative floor plans tools.

Challenges and Remedies in Interdisciplinary PG Programme

The world currently is reeling under acute shortage in essential resources for human existence due to growing population and elevated living standards. Today society at large demands more contributions from engineering community in terms of devising better and cost effective solutions to address existing problems. The engineering practice hence demands better skill sets that are honed to meet present day societal expectations. This situation demands improved teaching-learning methods that prepares engineering graduates to operate in multidisciplinary teams to accomplish the targeted solution or goal. The present work showcases implementation of effective pedagogical approach in Computational fluid dynamics (CFD) laboratory course prescribed for interdisciplinary PG Programme in Energy Systems Engineering. The course intends to enable students in usage of computational tools that includes commercial and open source software packages for fluid flow analysis. The CFDcourse has application in diverse engineering domains as a precursor for selection and optimization of functional elements in products that involve fluid flows.The course delivery posed several challenges due to diversity within student group and need of mathematical proficiency. The exercises designed in CFD lab-course related to execution of complete cycle of analysis taking into account formulation and solution of fluid flow and heat transfer aspects. The course thereby related to attainment of Programme outcomes (POs) covering areas of Research capabilities, Competence on use of modern computational tools, Multi-disciplinary team activity and communication aspects. The results obtained provide useful inputs to develop measures that will improve the delivery of the course for next batch of students opting the course.

Inhibition of human dyskerin as a new approach to target ribosome biogenesis.

The product of the DKC1 gene, dyskerin, is required for both ribosome biogenesis and telomerase complex stabilization. Targeting these cellular processes has been explored for the development of drugs to selectively or preferentially kill cancer cells. Presently, intense research is conducted involving the identification of new biological targets whose modulation may simultaneously interfere with multiple cellular functions that are known to be hyper-activated by neoplastic transformations. Here, we report, for the first time, the computational identification of small molecules able to inhibit dyskerin catalytic activity. Different in silico techniques were applied to select compounds and analyze the binding modes and the interaction patterns of ligands in the human dyskerin catalytic site. We also describe a newly developed and optimized fast real-time PCR assay that was used to detect dyskerin pseudouridylation activity in vitro. The identification of new dyskerin inhibitors constitutes the first proof of principle that the pseudouridylation activity can be modulated by means of small molecule agents. Therefore, the presented results, obtained through the usage of computational tools and experimental validation, indicate an alternative therapeutic strategy to target ribosome biogenesis pathway.