Bioinformatics and molecular modeling

A.Y. 2020/2021
Overall hours
BIO/10 CHIM/06 CHIM/08
Learning objectives
The purpose of this course is that participants gain knowledge on and understand:
- the prediction of the principal physicochemical and structural properties of pharmacological targets and of biotechnological drugs and products;
- the accuracy of in silico approaches used in the development of biotechnological drugs and products;
- the computational strategies for modelling targets, responsible for biological activity, simulating their interaction with biotechnological drugs and their molecular recognition mechanisms at an atomistic level;
methods to predict and validate the mechanism of action of biotechnological drugs and products, with particular attention to a better rational design of experiments on animal models, according to the 3Rs principle.
Expected learning outcomes
At the end of the course, the student is expected to know:
- the application of the computational methods used in biotechnological research;
to critically evaluate:
- the pros and cons of in silico prediction approaches used for developing biotechnological drugs and products;
to gain:
- the bases for deeply understanding computational methods and results described in scientific literature;
to obtain:
a multifaceted bioinformatics knowledgebase, useful for further student's personal study of this topic.
Course syllabus and organization

Single session

Lesson period
Second semester
For the Structural Bioinformatics teaching unit: about 50% of the lectures will take place remotely using Microsoft Teams and leaving recording on the Stream channel. About 50% of the lessons will consist of audio podcasts to introduce the supporting materials (books, slides, scientific publications). The activation of synchronous open classes is foreseen every time the students need to discuss each other and to have clarifications and insights from teachers. This organization will be discussed with students during the first lesson and modified if necessary.
For the Molecular Modelling teaching unit: if the health authorities will not allow the presence of students, the lessons will be held on the Zoom platform and can be followed both in synchrony on the basis of the established time, and asynchronously because they will be recorded and left available to students on the Ariel platform. The didactic program and examination methods will not be subject to changes. However, if the emergency situation continues, it will be possible to take the exam remotely via Zoom.
Course syllabus
The teaching unit of Structural Bioinformatics will provide an overview of bioinformatics techniques useful for dealing with the analysis of proteins, the main pharmacological targets and constituents of biotechnological drugs, introducing students to the logic and theoretical bases on which the most used computational approaches are based (3 CFU).
The teaching units of "Molecular modeling: basic methodologies" (2 CFU) and "Computational methodologies in biopharmaceutical development" (3 CFU) aim to provide the student with the knowledge necessary to understand the theoretical foundations and the fields in which computational chemistry applied to drug design can find valid applications both in the academic and industrial fields, so as to learn to critically evaluate the quality of the results and the limits of these methodologies.

Structural bioinformatics
1. Introduction to bioinformatics
2. Genome organization and evolution
3. Databases, archives and information retrieval
4. Substitution matrices, pairwise and multiple alignments, database search and phylogenetic trees
5. Protein structure and architecture
6. Protein structure prediction and validation: comparative modelling, threading and ab initio approaches
7. Introduction to systems biology

Data modeling in biotechnology

Molecular mechanics and dynamics
1. Elements of statistical thermodynamics
2. Introduction to Molecular Mechanics
a. The force fields
b. Solvent models and periodic conditions
c. Geometry optimization

3. Conformational search (CS)
a. Systematic CS methods
b. Stochastic CS methods

4. Molecular Dynamics (MD)
a. The equations of motion and the calculation of a trajectory
b. The microcanonical (NVE), canonical (NVT) and isothermal-isobaric (NPT) ensembles
c. trajectory analysis (energy profiles, RMSD, RMSF, geometrical parameters, hydrogen-bond, cluster analysis, principal component analysis)
d. Applications and limits of MD

5. Enhanced sampling techniques in MD simulations
a. Simulated annealing
b. Umbrella sampling
c. Replica exchange MD
d. Metadynamics
e. Accelerated MD

6. Calculation of free energy in complex systems
a. The potential of mean force (PMF)
b. Alchemical perturbations (Free Energy Perturbation and Thermodynamic Integration)
c. End-point methods (LIE and MM-PBSA)
Prerequisites for admission
It is a prerequisite to have gained at least:
3 ECTS of informatics
3 ECTS of mathematics and physics
4 ECTS of organic chemistry
6 ECTS in biochemistry, molecular biology or clinical biochemistry
Teaching methods
Frontal lessons.
Teaching Resources
Arthur M. Lesk, Introduction to Bioinformatics, Fifth Edition. Oxford University Press 2019.
Slides will be provided by the teacher after each lesson, and published on ARIEL web site.
Assessment methods and Criteria
The exam will be divided into two parts: an initial practical test and, if the test has a positive result, an oral test based on the verification of the comprehension and elaboration of the program carried out in class.
Data modeling in biotechnology
BIO/10 - BIOCHEMISTRY - University credits: 0
CHIM/06 - ORGANIC CHEMISTRY - University credits: 0
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
Lessons: 24 hours
Molecular mechanics and dynamics
BIO/10 - BIOCHEMISTRY - University credits: 0
CHIM/06 - ORGANIC CHEMISTRY - University credits: 0
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
Lessons: 16 hours
Professor: Contini Alessandro
Structural bioinformatics
BIO/10 - BIOCHEMISTRY - University credits: 0
CHIM/06 - ORGANIC CHEMISTRY - University credits: 0
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
Lessons: 24 hours
Professor: Eberini Ivano