OCommBIOSTEC 2018 Abstracts

Paper Nr: 24

SPRINT : A Server for Prediction of Protein Functional Sites from Sequence and Structure


Ghazaleh Taherzadeh, Yaoqi Zhou, Alan Wee-Chung Liew and Yuedong Yang

Abstract: Overwhelmed with genomic data, determining functions of previously unseen proteins is one of the most challenging problems. While most protein functions are often inferred from their homologous counterparts with known functions in other species, not all proteins have homologs whose functions are determined. Experimental determination of functions for millions of new proteins is certainly not practical because the possible functions are too many to be tested. Thus, it is highly desirable to have computational tools to prioritize possible functions for new proteins. Recently, we proposed machine learning-based tools called SPRINT that can predict putative binding sites of proteins interacting with small molecules as well as putative sites of post transnational modifications (PTMs). These prediction tools are available as an online server at: http://sparks-lab.org/.

Paper Nr: 26

Gene expression information improves reliability of receptor status in breast cancer patients


Michael Kenn

Abstract: Immunohistochemical (IHC) determination of receptor status in breast cancer patients is frequently inaccurate. Since it directs the choice of systemic therapy, it is essential to increase its reliability. We increase the validity of IHC receptor expression by additionally considering gene expression (GE) measurements. Crisp therapeutic decisions are based on IHC estimates, even if they are borderline reliable. We further improve decision quality by a responsibility function, defining a critical domain for gene expression. Refined normalization is devised to file any newly diagnosed patient into existing data bases. Our approach renders receptor estimates more reliable by identifying patients with questionable receptor status. The approach is also more efficient since the rate of conclusive samples is increased. We have curated and evaluated gene expression data, together with clinical information, from 2880 breast cancer patients. Combining IHC with gene expression information yields a method more reliable and also more efficient as compared to common practice up to now. Several types of possibly suboptimal treatment allocations, based on IHC receptor status alone, are enumerated. A ‘therapy allocation check’ identifies patients possibly miss-classified. Estrogen: false negative 8%, false positive 6%. Progesterone: false negative 14%, false positive 11%. HER2: false negative 2%, false positive 50%. Possible implications are discussed. We propose an ‘expression look-up-plot’, allowing for a significant potential to improve the quality of precision medicine. Methods are developed and exemplified here for breast cancer patients, but they may readily be transferred to diagnostic data relevant for therapeutic decisions in other fields of oncology.

Paper Nr: 27

Obtaining a stable complex between oxytocin and divalent zinc ion and testing it using molecular dynamic simulations.


Elisaveta Miladinova and Leandar Litov

Abstract: Oxytocin (OT) is a neurohypophysial hormone, which acts both on the peripheral tissues (hormonal), and as a neurotransmitter in the brain. It plays an important role in the control of uterine contractions during labor, secretion of milk and many social and behavioral functions. OT accomplishes its functions via interaction with specific oxytocin receptors, which belong to the rhodopsin - type (class I) group of G - protein coupled receptors (GPCRs). Data from experimental and theoretical studies have shown that the binding of divalent zinc ion to the oxytocin molecule drastically alters its conformation and ensures its correct location in the active receptor site. The formation of a stable complex between oxytocin and divalent zinc ion in an aqueous solution is an important condition necessary for hormone receptor binding. Still, crystallographic databases do not yet have information about the 3D structure of the complex. The aim of our study was to create a rigid structure between the human hormone oxytocin and the zinc ion and its confirmation using molecular dynamic simulations. A computer model of the hormone - metal complex was built to achieve this goal. The CHARMM 36 force field and artificial bonds were used to produce the structure with the octahedral orientation of the six carbonyl backbone oxygens of the oxytocin molecule surrounding the Zn2+ ion. The Gromacs software package was used to check the stability of the constructed oxytocin - zinc ion system by conducting 60 ns simulations in aqueous solution