Origins of life

Miller-Urey experiment 1953

A.M. Saittaa, F. Saijac,Miller experiments in atomistic computer simulations PNAS,111,38 (2014) 13768 Molecular Dynamics DFT – plane-wave/PBE method a reactants box MS01: 8 H2O, 8 NH3, 8 CH4, 10 CO, and 5 N2 molecules; intermediate MS02 box: containing nine molecules each of water, ammonia, formaldehyde, and hydrogen cyanide; the final products MS03 box: nine glycine and nine ammonia molecules Zero-field evolution MS01, MS03 no new compounds MS02 H2CO formaldehide + NH3 ammonia  HCONH2 formamide Electric field 0.35 V/Å MS01  HCOOH formic acid, HCONH2 formamide

MetD01 box: 1 CO, 1 NH3, 30 H2O  HCONH2 formamide

Miller-Urey experiment H2O, NH3, CH4, CO2, CO, H2, N2 glycine MS01: 8 H2O, 8 NH3, 8 CH4, 10 CO, and 5 N2 molecules MF01: 8 HCOOH formic acid, HCONH2 formamide, 8 H2O, 8 NH3, 8 CO (no inert CH4, N2)  glycine

NH=CH-(OH)3 Hydroxyglycine  NH=CH–COOH dehydroglycine  NH2-CH2–COOH glycine

THEORETICAL STUDY OF GLYCINE CONFORMERS, Journal of Theoretical and Computational Chemistry, Vol. 7, No. 4 (2008) 889 B3LYP/631+G* ∆E(kcal/mol) 0.00 0.45 0.43 1.44 1.44 1.44 1.47 5.27 2.77 5.80 11.56 7.63

Phys. Chem. Chem. Phys., 2004,6, 2563 MP2/6-311++G** kcal=4.2 kJ

Phys. Chem. Chem. Phys., 2013,15, 10094 hybrid CC/DFT

RNA World

Guanine, Adenine, and Hypoxanthine Production in UV-Irradiated Formamide Solutions: Relaxation of the Requirements for Prebiotic Purine Nucleobase Formation ChemBioChem 2010, 11, 1240

RNA or DNA Protein coating Viroid RNA don’t code any protein No protein coating RNA structurefunction 1971 Potato spindle disease viroid In humans Hepatitis D viroid enclosed in Hepatitis B virus capsid attacks liver cell 7S RNA RNA enzime or rybozyme (2006) 3D structure of the full-length hammerhead ribozyme

Self-cleaving RNA enzime

Prions – mad cow disease Stanley Prusiner, Nobel Prize in Physiology/Medicine in 1997 Challenged dogma DNA  RNA protein folding

Alzheimer’s disease Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP)

Amyloid β protein loop. The broken red  lines indicate a loop in the amyloid-B  protein that enables it to attach to  other proteins and form clumps that kill  brain cells.

Towards a Pharmacophore for Amyloid PNAS 2011

Short peptides self-assemble to produce catalytic amyloids, Nature Chemistry 6 (2014) 303–309   7 aminoacid short peptide Ac-IHIHIQI-CONH2 with Zn ions aggregate in prion-like fibrils can catalyze its self-ansembling and chemical reactions Enzyme for a model ester, p-nitrophenyl acetate

All 12 aminoacid short peptides - 20 at power 12 Chemical substances recognition Specific binding HFTFPQQQPPRP peptide binds to napthalene 34 times better than to benzene, or anthracene

molecular recognition

From short peptides to nanofibers to macromolecular assemblies in biomedicine Yihua Loo, Shuguang Zhang, Charlotte A.E. Hauser, Biotechnology Advances 30 (2012) 593

 Ho BK, Dill KA (2006) Folding Very Short Peptides Using Molecular Dynamics. PLoS Comput Biol 2(4) 133 peptide 8-mer peptides Amber 7 force field Mesostate [a] corresponds to a helical conformation, including the α helix, 310 helix, or π helix. Mesostate [b] corresponds to an extended β-strand conformation. Mesostate [l] corresponds to a left-handed helical conformation.  3^8 = 6,561 conformers 

Structure of the gas-phase glycine tripeptide Phys. Chem. Chem. Phys., 2010,12, 3463 B3LYP/6-31G(d) 20 most stable Gly–Gly–Gly conformers