Aug
13
Tue
2013
Invited Talk: A cost-effective approach to Protein Structure-guided Drug Discovery: Aided by Bioinformatics, Chemoinformatics and computational chemistry @ Sathyam Hall
Aug 13 @ 11:15 am – 11:40 am

kalKal Ramnarayan, Ph.D.
Co-founder President & Chief Scientific Officer, Sapient Discovery, San Diego, CA, USA


A cost-effective approach to Protein Structure-guided Drug Discovery: Aided by Bioinformatics, Chemoinformatics and computational chemistry

With the mapping of the human genome completed almost a decade ago, efforts are still underway to understand the gene products (i.e., proteins) in the human biological and disease pathways.  Deciphering such information is very important for the discovery and development of small molecule drugs as well as protein therapeutics for various human diseases for which no cure exists.  As an example, with more than 500 members, the kinase family of protein targets continues to be an important and attractive class for drug discovery.  While how many of the members in this family are actually druggable is still to be established, there are several ongoing efforts on this class of proteins across a broad spectrum of disease categories.  Even though in general the protein structural topology might looks similar, there are issues with respect selectivity of identified small molecule inhibitors when, the lead molecule discovery is carried out at the ATP binding site.  As an added complexity, allosteric modulators are needed for some of the members, but the actual site for such modulation on the protein target can not resolved with uncertainty.  In this presentation we will describe a bioinformatics and computational based platform for small molecule discovery for protein targets that are involved in protein-protein interactions as well as targets like kinases and phosphatases.  We will describe a computational approach in which we have used an informatics based platform with several hundred kinases to sort through in silico and identify inhibitors that are likely to be highly selective in the lead generation phase.  We will discuss the implication of this approach on the drug discovery of the kinase and phosphatase classes in general and independent of the disease category.

 

Invited Talk: Nanoscale Simulations – Tackling Form and Formulation Challenges in Drug Development and Drug Delivery @ Sathyam Hall
Aug 13 @ 2:15 pm – 2:40 pm

lalithaLalitha Subramanian, Ph.D.
Chief Scientific Officer & VP, Services at Scienomics, USA


Nanoscale Simulations – Tackling Form and Formulation Challenges in Drug Development and Drug Delivery

Lalitha Subramanian, Dora Spyriouni, Andreas Bick, Sabine Schweizer, and Xenophon Krokidis Scienomics

The discovery of a compound which is potent in activity against a target is a major milestone in Pharmaceutical and Biotech industry. However, a potent compound is only effective as a therapeutic agent when it can be administered such that the optimal quantity is transported to the site of action at an optimal rate. The active pharmaceutical ingredient (API) has to be tested for its physicochemical properties before the appropriate dosage form and formulation can be designed. Some of the commonly evaluated parameters are crystal forms and polymorphs, solubility, dissolution behavior, stability, partition coefficient, water sorption behavior, surface properties, particle size and shape, etc. Pharmaceutical development teams face the challenge of quickly and efficiently determining a number of properties with small quantities of the expensive candidate compounds. Recently the trend has been to screen these properties as early as possible and often the candidate compounds are not available in sufficient quantities. Increasingly, these teams are leveraging nanoscale simulations similar to those employed by drug discovery teams for several decades. Nanoscale simulations are used to predict the behavior using very little experimental data and only if this is promising further experiments are done. Another aspect where nanoscale simulations are being used in drug development and drug delivery is to get insights into the behavior of the system so that process failures can be remediated and formulation performance can be improved. Thus, the predictive screening and the in-depth understanding leads to experimental efficiency resulting in far-reaching business impacts.

With specific examples, this talk will focus on the different types of nanoscale simulations used to predict properties of the API in excipients and also provide insight into system behavior as a function of shelf life, temperature, mechanical stress, etc.

Delegate Talk: Insilico Analysis of hypothetical proteins from Leishmania donovani: A Case study of a membrane protein of the MFS class reveals their plausible roles in drug resistance @ Sathyam Hall
Aug 13 @ 3:35 pm – 3:50 pm
Delegate Talk: Insilico Analysis of hypothetical proteins from Leishmania donovani: A Case study of a membrane protein of the MFS class reveals their plausible roles in drug resistance @ Sathyam Hall | Vallikavu | Kerala | India

Nitish Sathyanrayanan, Sandesh Ganji and Holenarsipur Gundurao Nagendra.


Insilico Analysis of hypothetical proteins from Leishmania donovani: A Case study of a membrane protein of the MFS class reveals their plausible roles in drug resistance

Kala-azar or visceral leishmaniais (VL), caused by protozoan parasite Leishmania donovani, is one of the leading causes of morbidity and mortality in Bihar, India (Guerin et al. 2002; Mubayi et al. 2010). The disease is transmitted to the humans mainly by the vector, Phlebotmus argentipes, commonly known as Sand fly. The majority of VL (> 90%) occurs in only six countries: Bangladesh, India, Nepal, Sudan, Ethiopia and Brazil (Chappuis et al. 2007). In the Indian subcontinent, about 200 million people are estimated to be at risk of developing VL and this region harbors an estimated 67% of the global VL disease burden. The Bihar state only has captured almost 50% cases out of total cases in Indian sub-continent (Bhunia et al. 2013). ‘Conserved hypothetical’ proteins pose a challenge not just to functional genomics, but also to biology in general (Galperin and Koonin 2004). Leishmania donovani (strain BPK282A1) genome consists of a staggering ∼65% of hypothetical proteins. These uncharacterized proteins may enable better appreciation of signalling pathways, general metabolism, stress response and even drug resistance.