Use of virtual screening, flexible docking, and molecular interaction fields to design novel HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia

Dietary changes associated with drug therapy can reduce high serum cholesterol levels and dramatically decrease the risk of coronary artery disease, stroke, and overall mortality. Statins are hypolipemic drugs that are effective in the reduction of cholesterol serum levels, attenuating cholesterol synthesis in liver by competitive inhibition regarding the substrate or molecular target HMG-CoA reductase. We have herewith used computer-aided molecular design tools, i.e., flexible docking, virtual screening in large data bases, molecular interaction fields to propose novel potential HMG-CoA reductase inhibitors that are promising for the treatment of hypercholesterolemia.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson`s disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Computational design with flexible backbone sampling for protein remodeling and scaffolding of complex binding sites

Dissertation presented to obtain the Doutoramento (Ph.D.) degree in Biochemistry at the Instituto de Tecnologia Qu mica e Biol ogica da Universidade Nova de Lisboa

Design and Implementation of a Flexible Robot

This robot has low natural frequencies of vibration. Insights into the problems of designing joint and link flexibility are discussed. The robot has three flexible rotary actuators and two flexible, interchangeable links, and is controlled by three independent processors on a VMEbus. Results from experiments on the control of residual vibration for different types of robot motion are presented. Impulse prefiltering and slowly accelerating moves are compared and shown to be effective at reducing residual vibration.

Peptidomimetic design of unusual turns by incorporating flexible and rigid omega-amino acids simultaneously

The tripeptides Boc-Gly-Aib-m-ABA-OMe (I), Boc-beta Ala-Aib-m-ABA-OMe (II) and Boc-gamma Abu-Aib-rn-ABA-OMe (III) (Aib: alpha-aminoisobutyric acid, beta Ala: beta-alanine, gamma Abu: gamma-aminobutyric acid, m-ABA: meta-aminobenzoic acid) with homologated amino acids at the N-terminus, the rigid gamma-amino acid m-ABA at the C-terminus and the helicogenic Aib at the central position have been chosen to create unusual turns. Single crystal X-ray diffraction studies, solvent dependent NMR titrations and 2D NMR analysis reveal that peptides II and III adopt unusual turns of 11- and 12-membered rings stabilized by modified 4 -> 1 type intramolecular hydrogen bonds. Solution phase studies indicate that peptide I exists in the beta-turn conformation stabilized by 10-membered intramolecular hydrogen bonding.

Automatic design of decision-tree induction algorithms tailored to flexible-receptor docking data

Background: This paper addresses the prediction of the free energy of binding of a drug candidate with enzyme InhA associated with Mycobacterium tuberculosis. This problem is found within rational drug design, where interactions between drug candidates and target proteins are verified through molecular docking simulations. In this application, it is important not only to correctly predict the free energy of binding, but also to provide a comprehensible model that could be validated by a domain specialist. Decision-tree induction algorithms have been successfully used in drug-design related applications, specially considering that decision trees are simple to understand, interpret, and validate. There are several decision-tree induction algorithms available for general-use, but each one has a bias that makes it more suitable for a particular data distribution. In this article, we propose and investigate the automatic design of decision-tree induction algorithms tailored to particular drug-enzyme binding data sets. We investigate the performance of our new method for evaluating binding conformations of different drug candidates to InhA, and we analyze our findings with respect to decision tree accuracy, comprehensibility, and biological relevance. Results: The empirical analysis indicates that our method is capable of automatically generating decision-tree induction algorithms that significantly outperform the traditional C4.5 algorithm with respect to both accuracy and comprehensibility. In addition, we provide the biological interpretation of the rules generated by our approach, reinforcing the importance of comprehensible predictive models in this particular bioinformatics application. Conclusions: We conclude that automatically designing a decision-tree algorithm tailored to molecular docking data is a promising alternative for the prediction of the free energy from the binding of a drug candidate with a flexible-receptor.

Design of equalized ROADMs devices with flexible bandwidth based on LCoS technology

This paper describes the theory, design, applications and performance of a new Reconfigurable Add-drop Multiplexer (ROADM) with flexible bandwidth allocation. The device can address several wavelengths at the input to four output fibers, according to the holograms stored in a SLM (Spatial Light Modulator), where all the outputs are equalized in power. All combinations of the input wavelengths are possible at the different output fibers. Each fiber has assigned all the signals with the same bandwidth; the possible bandwidths are 12.5GHz, 25GHz, 50GHz and 100GHz, according to ITU-T 694.1 Recommendation. It is possible to route several signals with different bandwidth in real time thanks to Liquid Crystal over Silicon (LCoS) technology.

Airport Security: Passenger's Perception and Design Issues

The main goal of this thesis is to report patterns of perceived safety in the context of airport infrastructure, taking the airport of Bologna as reference. Many personal and environmental attributes are investigated to paint the profile of the sensitive passenger and to understand why precise factors of the transit environment are so impactful on the individual. The main analyses are based on a 2014-2015 passengers’ survey, involving almost six thousand of incoming and outgoing passengers. Other reports are used to implement and support the resource. The analysis is carried out by using a combination of Chi-square tests and binary logistic regressions. Findings shows that passengers result to be particularly affected by the perception of airport’s environment (e.g., state and maintenance of facilities, clarity and efficacy of information system, functionality of elevators and escalators), but also by the way how the passenger reaches the airport and the quality of security checks. In relation to such results, several suggestions are provided for the improvement of passenger satisfaction with safety. The attention is then focused on security checkpoints and related operations, described on a theoretical and technical ground. We present an example of how to realize a proper model of the security checks area of Bologna’s airport, with the aim to assess present performances of the system and consequences of potential variations. After a brief introduction to Arena, a widespread simulation software, the existing model is described, pointing out flaws and limitations. Such model is finally updated and changed in order to make it more reliable and more representative of the reality. Different scenarios are tested and results are compared using graphs and tables.

Design and construction of continously reinforced concrete airport pavements : final report /

Final report; August 1977.

Design of a display processing unit in a multi-terminal environment.

Photocopy of typescript.

The design and implementation of a calculator terminal /

"UIUCDCS-R-75-706"

The classification of soils for purposes of flexible pavement design.

Mode of access: Internet.

Flexible pavement design for airfields (elastic layered method).

"November 1989."