Current and Future Challenges in Modern Drug Discovery

Author(s):  
Christofer S. Tautermann
2019 ◽  
Vol 26 (21) ◽  
pp. 3890-3910 ◽  
Author(s):  
Branislava Gemovic ◽  
Neven Sumonja ◽  
Radoslav Davidovic ◽  
Vladimir Perovic ◽  
Nevena Veljkovic

Background: The significant number of protein-protein interactions (PPIs) discovered by harnessing concomitant advances in the fields of sequencing, crystallography, spectrometry and two-hybrid screening suggests astonishing prospects for remodelling drug discovery. The PPI space which includes up to 650 000 entities is a remarkable reservoir of potential therapeutic targets for every human disease. In order to allow modern drug discovery programs to leverage this, we should be able to discern complete PPI maps associated with a specific disorder and corresponding normal physiology. Objective: Here, we will review community available computational programs for predicting PPIs and web-based resources for storing experimentally annotated interactions. Methods: We compared the capacities of prediction tools: iLoops, Struck2Net, HOMCOS, COTH, PrePPI, InterPreTS and PRISM to predict recently discovered protein interactions. Results: We described sequence-based and structure-based PPI prediction tools and addressed their peculiarities. Additionally, since the usefulness of prediction algorithms critically depends on the quality and quantity of the experimental data they are built on; we extensively discussed community resources for protein interactions. We focused on the active and recently updated primary and secondary PPI databases, repositories specialized to the subject or species, as well as databases that include both experimental and predicted PPIs. Conclusion: PPI complexes are the basis of important physiological processes and therefore, possible targets for cell-penetrating ligands. Reliable computational PPI predictions can speed up new target discoveries through prioritization of therapeutically relevant protein–protein complexes for experimental studies.


2014 ◽  
Vol 490-491 ◽  
pp. 123-128 ◽  
Author(s):  
Nishka Ranjan ◽  
A.H. Manjunatha Reddy

The last two decades have witnessed a plethora of novel biomaterials that work significantly in the discovery of drugs and the point check of drugs, Biosensors. PLGA (Poly-(L-Lactide-co-glycolic Acid)), has already been shown to be a substrate for manufacture of substrates for OFETs, that in the future would be the forefront of electroceuticals. But, Polylactic Acid (PLA) derived and pegylated nanoparticles generated scaffolds, promote neural self-differentiation, nanowires derived from Polythiophene (PTs) can be utilised in the area of biosensors. Similarly, PT derived PEDOT:PSS(poly (3,4-ethylenedioxythiophene) poly (styrenesulfonate) polymer doped with appropriate cations is useful to manipulate directly the biological response of cells on the same grounds, organic electrochemical transistors (OECTs) based on PEDOTPSS coupled with bilayer lipid membranes (BLMs) were shown to act as ion-to-electron converters. A solid-state ion bipolar junction transistor (IBJT) has been developed to serve as a circuit element for neurotransmitter signal delivery. Consequently, the traditional drug discovery methods have far gone by. This era demands a much more modified and multiple disciplined methods for modern drug discovery. This review gives an insight and instance of this paradigm.


Author(s):  
Alexander I. Gray ◽  
John O. Igoli ◽  
RuAngelie Edrada-Ebel

Author(s):  
Sanchaita Rajkhowa ◽  
Ramesh C. Deka

Molecular docking is a key tool in structural biology and computer-assisted drug design. Molecular docking is a method which predicts the preferred orientation of a ligand when bound in an active site to form a stable complex. It is the most common method used as a structure-based drug design. Here, the authors intend to discuss the various types of docking methods and their development and applications in modern drug discovery. The important basic theories such as sampling algorithm and scoring functions have been discussed briefly. The performances of the different available docking software have also been discussed. This chapter also includes some application examples of docking studies in modern drug discovery such as targeted drug delivery using carbon nanotubes, docking of nucleic acids to find the binding modes and a comparative study between high-throughput screening and structure-based virtual screening.


Author(s):  
Giora Z. Feuerstein ◽  
Salvatore Alesci ◽  
Frank L. Walsh ◽  
J. Lynn Rutkowski ◽  
Robert R. Ruffolo

2018 ◽  
Vol 18 (20) ◽  
pp. 1755-1768 ◽  
Author(s):  
Ahmad Abu Turab Naqvi ◽  
Taj Mohammad ◽  
Gulam Mustafa Hasan ◽  
Md. Imtaiyaz Hassan

Protein-ligand interaction is an imperative subject in structure-based drug design and protein function prediction process. Molecular docking is a computational method which predicts the binding of a ligand molecule to the particular receptor. It predicts the binding pose, strength and binding affinity of the molecules using various scoring functions. Molecular docking and molecular dynamics simulations are widely used in combination to predict the binding modes, binding affinities and stability of different protein-ligand systems. With advancements in algorithms and computational power, molecular dynamics simulation is now a fundamental tool to investigative bio-molecular assemblies at atomic level. These methods in association with experimental support have been of great value in modern drug discovery and development. Nowadays, it has become an increasingly significant method in drug discovery process. In this review, we focus on protein-ligand interactions using molecular docking, virtual screening and molecular dynamics simulations. Here, we cover an overview of the available methods for molecular docking and molecular dynamics simulations, and their advancement and applications in the area of modern drug discovery. The available docking software and their advancement including application examples of different approaches for drug discovery are also discussed. We have also introduced the physicochemical foundations of molecular docking and simulations, mainly from the perception of bio-molecular interactions.


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