Molecular biophysics

A.Y. 2021/2022
Overall hours
Learning objectives
The course aims to provide students with a general understanding of the biophysical principles, the experimental techniques and the theoretical models enabling a quantitative description of intra- and inter-molecular interactions of biomolecules, with a main focus on nucleic acids and polypeptides. Primary objectives of the course are the understanding of the thermodynamic basis of equilibrium and kinetic phenomena related to biomolecular binding and conformational dynamics, the knowledge of advanced experimental techniques to quantitatively address the relevant parameters describing these phenomena, and, through practical training on computer programming, the use of computational tools to test the agreement of theoretical models with experimental data. The course also aims to convey the methodological process of physics, as the basis of a quantitative description of bimolecular behaviour.
Expected learning outcomes
At the end of the course the student will be able to:
- apply the concepts of thermodynamic and kinetic modelling to describe the intra- and inter-molecular interactions of proteins and DNA;
- describe the principles of fluorescence-based methods and biosensors to investigate biomolecular conformations and interactions at the nanoscale and correctly interpret and communicate results obtained with these methods;
- design and apply quantitative models to interpret the behaviour of biomolecular systems.
On successful completion of this course, students will gain:
- a critical ability to quantitatively address the behaviour of biomolecules and complex biomolecular systems;
- the capacity to access a wider scientific literature, addressing biological problems with biophysical tools and concepts, typically not included in a standard curriculum in biology.
Course syllabus and organization

Single session

Lesson period
Second semester
More specific information on the delivery modes of training activities for academic year 2021/22 will be provided over the coming months, based on the evolution of the public health situation.
Course syllabus
The topics are:
- Description of the dynamics of biomolecules in terms of fundamental interactions and diffusive motion.
- Thermodynamic equilibrium of the biomolecular conformations and interactions.
- Thermodynamics of DNA hybridization, protein folding and biomolecular recognition processes.
- Models based on diffusion equations, single molecule trajectories and rate equations for the description of the kinetics of intra- and inter-molecular interactions in proteins and nucleic acids.
- Phase separation of biomolecular compounds and spontaneous order at high concentration.
- Physical polymer models for the description of the conformation and intra-chain dynamics of polypeptides and nucleic acids.
- Supramolecular structures of nucleic acids.
- Experimental methods and models for the study of protein folding.
- Experimental methods based on fluorescence for the study of conformations and binding of biomolecules.
- Time-resolved fluorescence methods and single molecule fluorescence.
- Optical surface biosensors and models for analyzing results.
- Experimental methods based on the scattering of light.
- Molecular tools based on DNA nanotechnology.
- Use of software for numerical calculation of thermodynamic and kinetic parameters.
- Writing of Python programs for complex curve fitting based on models, simulation of simple polymeric and multi-particle models, quantitative analysis of results from fluorescence experiments, numerical resolution of kinetic models, analysis of binding curves obtained from biosensors.
Prerequisites for admission
General physics, molecular biology and biochemistry at bachelor level.
Teaching methods
The course is divided into classroom lectures, in which the topics are illustrated both with slides and on the blackboard. Exercises will be devoted to the development of case studies by computer-based calculation.
Teaching Resources
- Ken Dill, Sarina Bromberg, "Molecular Driving Forces: Statistical Thermodynamics in Biology, Chemistry, Physics, and Nanoscience", Garland Science, 2010
- Rob Phillips, Jane Kondev, Julie Theriot, Hernan Garcia, "Physical Biology of the Cell", Garland Science, 2012
- Slides of the lessons available on the website of the course
Assessment methods and Criteria
Learning assessment will be through written and oral exam at the end of the course. The written exam requires both the solution of problems with the description of the main steps and answering multiple choices tests. The written exam is aimed to broadly verify the understanding of concepts and definitions taught during the course. The duration of the written exam is one and a half hours. The oral exam will focus on the discussion of an individual homework report prepared by the student on a case study addressed during the computer-based exercises.
Examples of problems and questions and their evaluation will be provided during the course.
FIS/07 - APPLIED PHYSICS - University credits: 6
Practicals: 16 hours
Lessons: 40 hours
Educational website(s)
L.I.T.A. Segrate, Via F.lli Cervi 93