Molecular-Docking-Based Drug Design and Discovery

Currently 30-50% of drug targets are G Protein-Coupled Receptors (GPCRs). However, the clinical useful drugs for targeting GPCR have been limited by the lack of subtype selectivity or efficacy, leading to undesirable side effects. To develop subtype-selective GPCR ligands with desired molecular properties, better understanding is needed of the pharmacophore elements and of the binding mechanism required for subtype selectivity. To illustrate these issues, we describe here three successful applications to understand the binding mechanism associated with subtype selectivity: 5-HT2B (5-Hydroxytryptamine, 5-HT) serotonin receptor (HT2BR), H3 histamine receptor (H3HR) and A3 adenosine receptor (A3AR). The understanding of structure-function relationships among individual types and subtypes of GPCRs gained from such computational predictions combined with experimental validation and testing is expected the development of new highly selective and effective ligands to address such diseases while minimizing side-effects.

Smart, Innovative and Intelligent Technologies Used in Drug Designing

Smart and intelligent computational methods are essential nowadays for designing, manufacturing and optimizing new drugs. New and innovative computational tools and algorithms are consistently developed and applied for the development of novel therapeutic compounds in many research projects. Rapid developments in the architecture of computers have also provided complex calculations to be performed in a smart, intelligent and timely manner for desired quality outputs. Research groups worldwide are developing drug discovery platforms and innovative tools following smart manufacturing ideas using highly advanced biophysical, statistical and mathematical methods for accelerated discovery and analysis of smaller molecules. This chapter discusses novel innovative applications in drug discovery involving use of structure-based drug design which utilizes geometrical knowledge of the three-dimensional protein structures. It discusses statistical and physics based methods such as quantum mechanics and classical molecular dynamics which can also play a major role in improving the performance and in prediction of computational drug discovery. Lastly, the authors provide insights on recent developments in cloud computing with significant increase in smart and intelligent computational power thus allowing larger data sets to be analyzed simultaneously on multi processor cloud systems. Future directions for the research are outlined.

Molecular Dynamics Simulations for Biological Systems

Molecular dynamics simulation is an important tool to capture the dynamicity of biological molecule and the atomistic insights. These insights are helpful to explore biological functions. Molecular dynamics simulation from femto seconds to milli seconds scale give a large ensemble of conformations that can reveal many biological mysteries. The main focus of the chapter is to throw light on theories, requirement of molecular dynamics for biological studies and application of molecular dynamics simulations. Molecular dynamics simulations are widely used to study protein-protein interaction, protein-ligand docking, effects of mutation on interactions, protein folding and flexibility of the biological molecules. This chapter also deals with various methods/algorithms of protein tertiary structure prediction, their strengths and weaknesses.

Resealed Erythrocytes as Drug Carriers and Its Therapeutic Applications

In this pharma innovative world, there are more than 30 drug delivery systems. Today's due to lacking the target specificity, the present scenario about drug delivery is emphasizing towards targeted drug delivery systems. Erythrocytes are the most common type of blood cells travel thousands of miles from wide to narrow pathways to deliver oxygen, drugs and nutrient during their lifetime. Red blood cells have strong and targeted potential carrier capabilities for varieties of drugs. Drug-loaded carrier erythrocytes or resealed erythrocytes are promising for various passive and active targeting. Resealed erythrocyte have advantage over several drug carrier models like biocompatibility, biodegradability without toxic products, inert intracellular environment, entrapping potential for a variety of chemicals, protection of the organism against toxic effects of the drug, able to circulate throughout the body, ideal zero-order drug-release kinetics, no undesired immune response against encapsulated drug etc. Resealed erythrocytes are rapidly taken up by macrophages of the Reticuloendothelial System (RES) of the liver, lung, and spleen of the body and hence drugs also. Resealed erythrocytes method of drugs delivery is secure and effective for drugs targeting specially for a longer period of time. This chapter will explain the different method of drug loading for resealed erythrocytes, their characterization, and applications in various therapies and associated health benefits.

Hybrid Plasmonic Nanostructures

Plasmonic hybrid nanostructure including Semiconductor-metallic nanoparticles, and graphene-plasmonic nanocomposites have great potential to be used as photocatalyst for hydrogen production and for photodegradation of organic waste. Also, they are potential candidate as active materials in photovoltaic devices. Plasmonic-magnetic nanocomposites could be used in photothermal therapy and biomedical imaging. This chapter will focus on the environmental impact of these materials and their in-vitro and in-vivo toxicity. In addition, the applications of these hybrid nanostructures in energy and environment will be discussed in details.

QSAR-Based Studies of Nanomaterials in the Environment

Nanotechnology is a newly emerging field, posing substantial impacts on society, economy, and the environment. In recent years, the development of nanotechnology has led to the design and large-scale production of many new materials and devices with a vast range of applications. However, along with the benefits, the use of nanomaterials raises many questions and generates concerns due to the possible health-risks and environmental impacts. This chapter provides an overview of the Quantitative Structure-Activity Relationships (QSAR) studies performed so far towards predicting nanoparticles' environmental toxicity. Recent progresses on the application of these modeling studies are additionally pointed out. Special emphasis is given to the setup of a QSAR perturbation-based model for the assessment of ecotoxic effects of nanoparticles in diverse conditions. Finally, ongoing challenges that may lead to new and exciting directions for QSAR modeling are discussed.

Strategies for Expanding Access and Improving the Quality of Pharmaceutical Services

Pharmaceutical services are among the most accessible healthcare assistance systems worldwide, being provided generally in enterprises like Drugstores and Compounding Pharmacies. Pharmacists are highly accessible healthcare professionals considering also the availability, geographic distribution and location of pharmaceutical enterprises. However, there are several challenges for providing these services for patients with limitations such as low education, difficulties on reaching the Pharmacist, and the need for individualized monitoring (due to the complexity of therapy). Reports of low quality services are growing worldwide, and in order to expand access and improve the quality of pharmaceutical services, Pharmacists must move from being medication dispensers with focus in administrative management to a clinically-oriented practice with a humanistic view. The aim of this chapter is to make an approach on the implementation of effective strategies and ways to improve the quality of Pharmacists' work as specialized healthcare providers.

The Comparison of Docking Search Algorithms and Scoring Functions

This chapter, composed of two parts, firstly provides molecular docking overview and secondly two molecular docking case studies are described. In overview, basic information about molecular docking are presented such as description of search algorithms and scoring functions applied in various docking programs. Brief description of methods utilized in some of the most popular docking programs also applied in our experimental work is provided. AutoDock, CDOCKER, GOLD, FlexX and FRED were used for docking studies of the DC-SIGN protein, while GOLD was further used for docking studies of cathepsin K protein. Methods and results of our studies with their contribution to science and medicine are presented. Content of the chapter is therefore appropriate for public of Medicinal and Organic Chemistry as an overview of docking studies, and also for Computational Chemists at the beginning of their work as the introduction to application of molecular docking programs.

Protein Ligand Interaction Fingerprints

A most challenging part in docking-based virtual screening is the scoring functions implemented in various docking programs in order to evaluate different poses of the ligands inside the binding cavity of the receptor. Precise and trustable measurement of ligand-protein affinity for Structure-Based Virtual Screening (SB-VS) is therefore, an outstanding problem in docking studies. Empirical post-docking filters can be helpful as a way to provide various types of structure-activity information. Different types of interaction have been presented between the ligands and the receptor so far. Based on the diversity and importance of PLIF methods, this chapter will focus on the comparison of different protocols. The advantages and disadvantages of all methods will be discussed explicitly in this chapter as well as future sights for further progress in this field. Different classifications approaches for the protein-ligand interaction fingerprints were also discussed in this chapter.

An Overview of Therapeutic Applications

Over the last few years' great advances have been made on the development drug delivery systems for different purposes for targeting the diseased conditions. Novel drug delivery originates from polymers or associated with some devices is generally related with the emergence of novel characteristics. These changes are what eventually comprise the value of drug delivery system and Novel drug delivery system. Novel properties become existed without making new materials. Novel drug delivery system comparable to traditional system, following Targeted Drug Delivery System (TDDS) is also called targeting drug system. A new drug delivery system makes the drugs densely gather pathological-change structures, and has an improved healing effect and less toxic side effects. The drugs can improve the strength of pharmacological action and reduce the bad effect all over the body, for they release in the target organs.