C7790 Introduction to Molecular Modelling -1Lesson
1
Computational Chemistry
(Molecular Modelling)
C7790 Introduction to Molecular
Modelling
TSM Modelling Molecular Structures
C9087 Computational Chemistry for Structural Biology
Petr Kulhánek
kulhanek@chemi.muni.cz
National Centre for Biomolecular Research, Faculty of Science
Masaryk University, Kamenice 5, CZ-62500 Brno
PS/2022 Present Form of Teaching: Rev4
C7790 Introduction to Molecular Modelling -2Computational
chemistry
(bio)chemical problem
(behavior of the chemical system at
the macroscopic level)
molecular nature
(behavior of the chemical system at
the microscopic level)
experiment
C7790 Introduction to Molecular Modelling -3Computational
chemistry
(bio) chemical problem
(behavior of the chemical system at
the macroscopic level)
molecular nature
(behavior of the chemical system at
the microscopic level)
experiment
)()(ˆ rr kkk EH  =
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−=
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−
−=
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Tk
U
b
b
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C7790 Introduction to Molecular Modelling -4Computational
chemistry
(bio) chemical problem
(behavior of the chemical system at
the macroscopic level)
molecular nature
(behavior of the chemical system at
the microscopic level)
experiment
calculation/simulation

−
−=
k
Tk
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b
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k
eTkA ln
)()(ˆ rr kkk EH  =
i
i
i
r
V
dt
rd
m
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?
C7790 Introduction to Molecular Modelling -5Reality
vs Simulation
Is it possible to accurately simulate the reality around us?
C7790 Introduction to Molecular Modelling -6Task
I
Is it possible to accurately simulate the reality around us?
How many molecules does 180
mL of water contain at room
temperature?
How much computer memory will be needed to store the position information of all
atoms, including their velocities, using real numbers with single precision?
single precision real number = 4 Bytes
C7790 Introduction to Molecular Modelling -7Task
II
Is it possible to accurately simulate the reality around us?
How much machine time does 1 s long
simulation with the development of the
molecular system (H2O) take?
➢ The fastest molecular motion in H2O is the vibration of OH bonds.
➢ What is the period of this vibration (Use NIST Chemistry WebBook)?
➢ Each period needs to be discretized by at least 10 frames (snapshots) (see Molecular
Dynamics later).
➢ Computation of each frame takes approximately 1 ms of computer time.
C7790 Introduction to Molecular Modelling -8-
Solution
Task I (180 mL H2O)
𝑁 𝑊𝐴𝑇 ≈ 6𝑥1024
𝑁 𝑚𝑒𝑚 ≈ 432 000 000 000 000 000 000 000 000 𝐵
Task II (1s long simulation of H2O)
𝑡 ≈ 1012 𝑠 = 31 709 years
෤𝜐 = 3756 𝑐𝑚−1 𝜐 = 113 𝑇𝐻𝑧 𝑇 = 8.8 𝑓𝑠 ≈ 10 𝑓𝑠
C7790 Introduction to Molecular Modelling -9Reality
vs Simulation
Is it possible to accurately simulate the reality around us?
Unfortunately, no :-(
Problem Result
experiment
Why?
⚫ incomplete theory
⚫ insufficient performance of current and future (?) computers
Solution ...
⚫ use approximation for solution of problems using the available computing
capacity
C7790 Introduction to Molecular Modelling -10Reality
vs Simulation
Problem
Model Result
approximation
Result
experiment
validation
!!!!
approximation
Why?
⚫ incomplete theory
⚫ insufficient performance of current and future (?) computers
Solution ...
⚫ use approximation for solution of problems using the available computing
capacity
Is it possible to accurately simulate the reality around us?
Unfortunately, no :-(
Model chemistry
(Calculation method)
C7790 Introduction to Molecular Modelling -11Reality
vs Simulation
Problem
Model Result
approximations
Result
Result
experiment
approximation
prediction
Why?
⚫ incomplete theory
⚫ insufficient performance of current and future (?) computers
Solution ...
⚫ use approximation for solution of problems using the available computing
capacity
Is it possible to accurately simulate the reality around us?
Unfortunately, no :-(
Model chemistry
(Calculation method)
C7790 Introduction to Molecular Modelling -12Experimental
sources for validation
Comparison of predicted structures with experimental structures
▪ 3D structure (X-ray, docking)
▪ shape (cryogenic electron microscopy)
▪ geometric parameters
▪ distances (NMR)
▪ radial distribution function (X-ray scattering, neutron scattering)
Properties of molecules
▪ electron spectra (UV/VIS spectroscopy)
▪ vibrational spectra (IR spectroscopy)
▪ dipole moment
▪ diffusion coefficient
▪ chemical shifts, spin-spin interaction constants (NMR)
Comparison of calculated and experimental thermodynamic and kinetic data
▪ enthalpy (isothermal titration calorimetry - ITC)
▪ entropy (ITC)
▪ free energy (Gibbs, Helmholtz) (ITC, kinetic measurements)
C7790 Introduction to Molecular Modelling -13Computational
chemistry
computational
chemistry
experiment
theory
Computational chemistry is a branch of chemistry that uses
computers to solve chemical problems. It uses the results of
theoretical chemistry implemented in powerful computer
programs designed to calculate the structure, properties and
reactivity of molecules and solids.
http: // www.wikipedia.org
C7790 Introduction to Molecular Modelling -14Multidisciplinary
discipline
algorithms, CPU / GPU,
cluster / grid,
symbolic calculations
analytical solution,
numerical solutions,
approximation
theory, approximation
(bio)chemical problems,
experiments,
verification
computational
chemistry
C7790 Introduction to Molecular Modelling -15Importance
of computational chemistry
computational
chemistry
experiment
theory
"resolution”"accuracy”
C7790 Introduction to Molecular Modelling -16Importance
of computational chemistry
computational
chemistry
experiment
theory
"resolution”"accuracy”
Computational chemistry can work with
single atom resolution.
C7790 Introduction to Molecular Modelling -17Experiment
vs simulation
hypothesis
result
problem
knowledge
experiments
simulations
▪reality around us
▪ resolution
▪ expensive, dangerous,
too complicated to
implement
▪ resolution (mostly atomic resolution)
▪ any conceivable arrangement
▪ model
C7790 Introduction to Molecular Modelling -18-
Summary
Computational chemistry (molecular modelling):
➢ it is an interdisciplinary scientific discipline combining current knowledge
of physics, chemistry, mathematics and computer sciences for
computational study of structure, properties, and reactivity molecular
systems
➢ it uses approximate models and calculation procedures
➢ it requires verification/calibration of employed models and
computational procedures against experimental data
➢ it can reach both qualitative (mostly) and quantitative results (according
to models used)
➢ it typically employs models with atomic resolution
During the lecture we will get acquainted with methods enabling the study of systems
containing up to 1,000,000 atoms in the time scale a few microseconds.
C7790 Introduction to Molecular Modelling -19Nobel
Prize in Chemistry 1998/2013
The Nobel Prize in Chemistry 1998 was divided
equally between
Walter Kohn for his development of the
density-functional theory and
John A. Pople for his development of
computational methods in quantum
chemistry
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1998/
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2013/
Development of Multiscale Models for
Complex Chemical Systems