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In Silico Pharmacology

Monika Marczak, Krystyna Okoniewska, Tomasz Grabowski
BACKGROUND: Total body clearance of biological drugs is for the most part dependent on the receptor mechanisms (receptor mediated clearance) and the concentration of antibodies aimed at administered drug - anti-drug-antibodies (ADA). One of the significant factors that induces the increase of ADA level after drug administration could be the aggregates present in the finished product or formed in the organism. Numerous attempts have been made to identify the sequence fragments that could be responsible for forming the aggregates - aggregate prone regions (APR)...
December 2016: In Silico Pharmacology
Tahirah Yasmin, Salma Akter, Mouly Debnath, Akio Ebihara, Tsutomu Nakagawa, A H M Nurun Nabi
PURPOSE: Campylobacter jejuni is the one of the leading causes of bacterial diarrheal illness worldwide. This study aims to design specific epitopes for the utility of designing peptide vaccine(s) against C. jejuni by targeting invasive, virulent and membrane associated proteins like FlaA, Cia, CadF, PEB1, PEB3 and MOMP. METHODS: In the present study, various immunoinformatics approaches have been applied to design a potential epitope based vaccine against C. jejuni...
December 2016: In Silico Pharmacology
Jinhyuk Kim, Toru Nakamura, Yoshiharu Yamamoto
Many biomarkers from genetic, neuroimaging, and biological/biochemical measures have been recently developed in order to make a shift toward the objective evaluation of psychiatric disorders. However, they have so far been less successful in capturing dynamical changes or transitions in pathological states, such as those occurring during the course of clinical treatments or pathogenic processes of disorders. A momentary biomarker is now required for objective monitoring of such dynamical changes. The development of ecological momentary assessment (EMA) allows the assessment of dynamical aspects of diurnal/daily clinical conditions and subjective symptoms...
December 2016: In Silico Pharmacology
Elliot Offman, Colin Phipps, Andrea N Edginton
PURPOSE: Physiologically-based pharmacokinetic (PBPK) models provide a rational mechanistic approach for predicting the time course of macromolecules in plasma. Population PBPK models for large molecules necessitate incorporation of lymphatic circulation to mechanistically account for biodistribution. Moreover, characterization of subcutaneous absorption requires consideration of the microvascular transit from the injection site to the systemic circulation. A PBPK model for a pegylated peptide conjugate, previously developed for primates, was modified to describe the lymphatic uptake in a population of humans by incorporation of interindividual variability in the lymphatic circulation and a unique lymphatic drainage compartment (LDC)...
December 2016: In Silico Pharmacology
Avanthika Venkatachalam, Abhinav Parashar, Kelath Murali Manoj
PURPOSE: The currently held mechanistic understanding of microsomal cytochrome P450s (CYPs) seeks that diverse drug molecules bind within the deep-seated distal heme pocket and subsequently react at the heme centre. To explain a bevy of experimental observations and meta-analyses, we indulge a hypothesis that involves a "diffusible radical mediated" mechanism. This new hypothesis posits that many substrates could also bind at alternate loci on/within the enzyme and be reacted without the pertinent moiety accessing a bonding proximity to the purported catalytic Fe-O enzyme intermediate...
December 2016: In Silico Pharmacology
Douglas Steinley, Sean P Lane, Kenneth J Sher
PURPOSE: Contemporary approaches to clinical diagnosis have not adequately exploited state-of-the-art empirical techniques in deriving diagnostic criterion sets that are statistically optimal based on 1) relevant external indicators and 2) replicability across data sets. We provide a proof of concept that optimal criterion sets can be derived with respect to alcohol use disorder (AUD) diagnosis that are both more efficient and precise than current systems. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions we selected chronicity (i...
December 2016: In Silico Pharmacology
Jamil A Shilpi, Mohammad Tuhin Ali, Sanjib Saha, Shihab Hasan, Alexander I Gray, Véronique Seidel
PURPOSE: There is an urgent need to discover and develop new drugs to combat Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) in humans. In recent years, there has been a renewed interest in the discovery of new anti-TB agents from natural sources. In the present investigation, molecular docking studies were carried out on two ellagic acid derivatives, namely pteleoellagic acid (1) isolated from Ludwigia adscendens, and 3,3'-di-O-methyl ellagic acid 4-O-α-rhamnopyranoside (2) isolated from Trewia nudiflora, to investigate their binding to two enzymes involved in M...
December 2015: In Silico Pharmacology
Padmaa M Paarakh, Dileep Chandra Sreeram, Shruthi S D, Sujan P S Ganapathy
BACKGROUND: Piper nigrum [Piperaceae], commonly known as black pepper is used as medicine fairly throughout the greater part of India and as a spice globally. PURPOSE: To isolate piperine and evaluate in vitro cytotoxic [antiproliferative] activity and in silico method. METHODS: Piperine was isolated from the fruits of P.nigrum. Piperine was characterized by UV,IR, (1)H-NMR, (13)C-NMR and Mass spectrum. Standardization of piperine was done also by HPTLC fingerprinting...
December 2015: In Silico Pharmacology
Pär Matsson, Christel A S Bergström
Transport proteins are important mediators of cellular drug influx and efflux and play crucial roles in drug distribution, disposition and clearance. Drug-drug interactions have increasingly been found to occur at the transporter level and, hence, computational tools for studying drug-transporter interactions have gained in interest. In this short review, we present the most important transport proteins for drug influx and efflux. Computational tools for predicting and understanding the substrate and inhibitor interactions with these membrane-bound proteins are discussed...
December 2015: In Silico Pharmacology
Arafat Rahman Oany, Tahmina Sharmin, Afrin Sultana Chowdhury, Tahmina Pervin Jyoti, Md Anayet Hasan
PURPOSE: Ebola virus (EBOV) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. Although, medical technology has tried to handle the problems, there is no Food and Drug Administration (FDA)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of Ebola virus disease (EVD). METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV...
December 2015: In Silico Pharmacology
Madison Wynne El-Saadi, Tara Williams-Hart, Brian A Salvatore, Elahe Mahdavian
PURPOSE: For 30 years nature has provided a plethora of natural products with potential meaningful anti-cancer activity. Fusarochromanone (FC101a) is a small molecule fungal metabolite exhibiting potent in-vitro growth inhibitory effects and is capable of inducing apoptosis, suppressing angiogenesis and tumorigenesis, and inhibiting endothelial cell growth in multiple cancer cell lines. Despite all we know regarding FC101a, the mechanism of action and molecular target(s) of this compound have remained an enigma...
December 2015: In Silico Pharmacology
Hemant Sarin
PURPOSE: Neutral small hydrophiles are permeable to varying degrees, across the aqueous pores of phospholipid bilayer protein channels, with their potential for permeation into cells being predictable, on the basis of hydrophilicity and size. Here, it is hypothesized that permeation thresholds for small hydrophiles, across capillary zona occludens tight junction and inter-epithelial junction pore complexes are predictable, on the basis of predicted hydrophilicity in context of predicted molecular size and charge distribution, as are those of cations and anions, on the basis of predicted ionization in context of predicted atomic size...
December 2015: In Silico Pharmacology
Chelsea N Powers, William N Setzer
PURPOSE: The purpose of this study is to use a molecular docking approach to identify potential estrogen mimics or anti-estrogens in phytochemicals found in popular dietary herbal supplements. METHODS: In this study, 568 phytochemicals found in 17 of the most popular herbal supplements sold in the United States were built and docked with two isoforms of the estrogen receptor, ERα and ERβ (a total of 27 different protein crystal structures). RESULTS: The docking results revealed six strongly docking compounds in Echinacea, three from milk thistle (Silybum marianum), three from Gingko biloba, one from Sambucus nigra, none from maca (Lepidium meyenii), five from chaste tree (Vitex agnus-castus), two from fenugreek (Trigonella foenum-graecum), and two from Rhodiola rosea...
2015: In Silico Pharmacology
Nathaniel Stanley, Gianni De Fabritiis
Molecular dynamics simulations hold the promise to be an important tool for biological research and drug discovery. Historically, however, there were several obstacles for it to become a practical research tool. Limitations in computer hardware had previously made it difficult to simulate for long enough to see interesting biological processes. Recent improvements in hardware and algorithms have largely removed this issue, leaving data analysis as the main obstacle. Advances in Markov state modeling appear to be on the way to remove this obstacle...
2015: In Silico Pharmacology
Hamid R Noori, Rainer Spanagel
No abstract text is available yet for this article.
2015: In Silico Pharmacology
Kuteesa R Bisaso, Joel S Owen, Francis W Ojara, Proscovia M Namuwenge, Apollo Mugisha, Lawrence Mbuagbaw, Livingstone S Luboobi, Jackson K Mukonzo
No abstract text is available yet for this article.
2015: In Silico Pharmacology
Marios Spanakis, Kostas Marias
PURPOSE: Gadofosveset is a Gd-based contrast agent used for magnetic resonance imaging (MRI). Gadolinium kinetic distribution models are implemented in T1-weighted dynamic contrast-enhanced perfusion MRI for characterization of lesion sites in the body. Physiology changes in a disease state potentially can influence the pharmacokinetics of drugs and to this respect modify the distribution properties of contrast agents. This work focuses on the in silico modelling of pharmacokinetic properties of gadofosveset in different population groups through the application of physiologically-based pharmacokinetic models (PBPK) embedded in Simcyp® population pharmacokinetics platform...
December 2014: In Silico Pharmacology
Hans-Joachim Wittmann, Roland Seifert, Andrea Strasser
PURPOSE: It was shown by several experimental studies that some G protein coupled receptors (GPCR) are sensitive to sodium ions. Furthermore, mutagenesis studies or the determination of crystal structures of the adenosine A2A or δ-opioid receptor revealed an allosteric Na(+) binding pocket near to the highly conserved Asp(2.50). Within a previous study, the influence of NaCl concentration onto the steady-state GTPase activity at the human histamine H3 receptor (hH3R) in presence of the endogenous histamine or the inverse agonist thioperamide was analyzed...
December 2014: In Silico Pharmacology
Pramod C Nair, John O Miners
Molecular dynamics (MD) simulation is an emerging in silico technique with potential applications in diverse areas of pharmacology. Over the past three decades MD has evolved as an area of importance for understanding the atomic basis of complex phenomena such as molecular recognition, protein folding, and the transport of ions and small molecules across membranes. The application of MD simulations in isolation and in conjunction with experimental approaches have provided an increased understanding of protein structure-function relationships and demonstrated promise in drug discovery...
2014: In Silico Pharmacology
Kuteesa R Bisaso, Joel S Owen, Francis W Ojara, Proscovia M Namuwenge, Apollo Mugisha, Lawrence Mbuagbaw, Livingstone S Luboobi, Jackson K Mukonzo
PURPOSE: Plasma albumin, a biomarker for hepatic function, is reported to correspondingly decrease in concentration as disease severity increases in chronic infections including HIV and TB. Our objective was to develop a semi-mechanistic disease progression model to quantify plasma albumin concentration changes during TB and HIV therapy and identify the associated covariate factors. METHODS: Plasma albumin concentration data was collected at specified times for 3 months from 262 HIV participants receiving efavirenz based anti retroviral therapy...
2014: In Silico Pharmacology
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