Chapter 1 Basic concepts of Molecular Biology

OutlineTo present basic concepts of molecular biology

•Biological background•Literature on computational molecular biology

To point out some of the most notable exceptions to general rules, but not all--nothing is 100% valid in molecular biology

Three molecules we will study

DNA A string over alphabet {A,C,G,T}

RNA Primary structure – a string over alphabet {A,C,G,U} Secondary and tertiary structures

Protein Primary structure – a string over alphabet

{A,R,N,D,C,Q,E,G,H,I,L,K,M,F,P,S,T,W,Y,V} Secondary and tertiary structures

Central dogma of molecular biology

DNA: store genetic information; regular double helix structure building blocks: 4 nucleotides

A,C,G, and T (Adenine, Cytosine, Guanine, Thymine)

RNA: intermediate for protein synthesis (messenger RNA), catalytic and regulatory function (non-coding RNA) building blocks: 4 nucleotides

A,C,G, and U (U=Uracil) and some rare other

nucleotides Protein: catalytic and regulatory

function (`enzymes') building blocks: 20 amino acids + 1

rare aa

DNA makes RNA makes protein

1.1 Life

living and nonliving things Difference

• Living: active– to move, reproduce, grow, eat1. Act the way they do due to a complex array of

chemical reactions that occur inside them2. Constantly exchanging matter and energy with its

surroundings• Dead: in equilibrium with its surrounding• Exceptions: seeds, and viruses / inactive but not dead

Commonness• Composed by same atoms, and conforming to same

physical and chemical rules

1.1 Life

Proteins and nucleic acids main actors in the chemistry of life: molecules Proteins

• 1) responsible for what a living being is and does in physical sense;

• 2) Russell Doolittle: “we are our proteins” nucleic acids

• 1) encode the information necessary to produce proteins;

• 2) responsible for passing along this “recipe (prescription)” to subsequent generations

molecular biology research understanding of the structure and function of proteins

and nucleic acids --the molecules as fundamental objects of this course

1.2 proteins proteins: most substances in our bodies;

many kinds; functions Enzymes: catalysts of chemical reactions;

roles:

A protein: a chain of simpler molecules of amino acids, AA

20 different AAs exception: a few nonstandard amino acids. How to get protein?

Ribosome (核糖体 ): a cell structure to produce protein / assemble amino acids one by one

examples of amino acids: alanine and threonine

• one alpha carbon, or Cα• An amino group (NH2)• a hydrogen atom: H• a carboxy group: COOH• a side chain: e.g. : 1)glycine: one hydrogen atom

2)tryptophan: two carbon rings

Residue

Protein and Amino Acids

Typically, the number of residues of a protein is 300.

A protein sequence

>gi|7228451|dbj|BAA92411.1| EST AU055734(S20025) corresponds to a region …

MCSYIRYDTPKLFTHVTKTPPKNQVSNSINDVGSRRATDRSVASCSSEKSVGTMSVKNASSISFEDIEKSISNWKIPKVN

IKEIYHVDTDIHKVLTLNLQTSGYELELGSENISVTYRVYYKAMTTLAPCAKHYTPKGLTTLLQTNPNNRCTTPKTLKWD

EITLPEKWVLSQAVEPKSMDQSEVESLIETPDGDVEITFASKQKAFLQSRPSVSLDSRPRTKPQNVVYATYEDNSDEPSI

SDFDINVIELDVGFVIAIEEDEFEIDKDLLKKELRLQKNRPKMKRYFERVDEPFRLKIRELWHKEMREQRKNIFFFDWYE

SSQVRHFEEFFKGKNMMKKEQKSEAEDLTVIKKVSTEWETTSGNKSSSSQSVSPMFVPTIDPNIKLGKQKAFGPAISEEL

VSELALKLNNLKVNKNINEISDNEKYDMVNKIFKPSTLTSTTRNYYPRPTYADLQFEEMPQIQNMTYYNGKEIVEWNLDG

FTEYQIFTLCHQMIMYANACIANGNKEREAANMIVIGFSGQLKGWWNNYLNETQRQEILCAVKRDDQGRPLPDRDGNGNP

TELKEGFHMEEKDEPIQEDDQVVGTIQKYTKQKWYAEVMYRFIDGSYFQHITLIDSGADVNCIREDEILDQLVQTKREQV

VNSIYLHDNSFPKSMDLPDQKITEKRAKLQDIPHHEERLLDYREKKSRDGQDKLPMEVEQSMATNKNTKILLRAWLLST

A protein sequence may have a few hundreds to several thousands amino acids.

The basic hemical structure of an amino acid. Carbon atoms are black,Oxygen is dark grey, Nitrogen light grey, and hydrogen white.

Backbone

A polypeptide chain. The R1 side chains identify the component amino acids. Atoms inside each quadrilateral are on the same plane, which can rotate according to angles and .

1.2 proteins Primary structure: a linear sequence of residues; peptide

bonds Fold in three dimensions

• secondary: interactions between backbone atoms; “local” structure; helices: side chains move

• tertiary : packing on secondary• quaternary structures: packing on different

proteins

Protein structure

1.2 proteins Structure prediction

Secondary structure prediction

--exact folding: to specify all - pairs in a protein three-dimensional structure prediction

--determining the folding of a protein is one of the main research areas in molecular biology in that:

• 1)shape related to function• 2)20 amino acids->3D-structure• 3)no simple / accurate method: determining 3D-structure.• --try to predict a molecule’s structure from its Primary

structure shape determines to function

a folded protein has an irregular shape: bind to some other specific molecules

the kinds of molecules a protein can bind to depend on its shape

1.2 protein binding

1.3 NUCLEIC ACIDS / 1.3.1 DNA Two kinds of nucleic acids in living organisms

RNA: ribonucleic acids DNA: deoxyribonucleic acids

Strand and Orientation DNA: a molecule; a chain of simple molecules; Double

chain; repetitions of the same basic unit->a sugar: 2’-deoxyribose

(脱氧核糖 ) attached to a phosphate residue (磷酸残基 ) -> sugar molecule: 5 carbon atoms 1’-5’

the backbone: 3’ carbon of one unit and 5’ of next unit. Orientation: 5’->3’; canonical: (1)technical paper (2) book

(3) sequence database file

DNA: deoxyribose sugar

Ribose 2’-deoxyribose

1.3.1 DNA Bases (碱基 )

Base:1’C atom; 4 kinds• A-T; C-G• A,G : purines (嘌呤 ); C,T: pyrimidines （嘧啶）

Complementarity of organic bases

1.3.1 DNA complement; complementary bases; bp

two strands: a helical structure: discovered by James Watson and Francis Crick in 1953

Watson—Crick base pairs: pairs A and T; C and G bp: unit of length / a piece of DNA is 100,000 bp long or 100kb.

Antiparallel; Reverse complementation; replicate5’ … TACTGAA … 3’3’ … ATGACTT … 5’

Given one DNA chain “AGACGT”, can we get the complementary chain?

1.3.1 DNA Reverse complementation: operation to

infer the sequence of one strand given the other: s→s’ →s bar / AGACGT-TGCAGA-ACGTCT (always 5-3)

replicate: It is precisely this mechanism that allow DNA in a cell to replicate, therefore allowing an organism that starts its life as one cell to grow into billions of other cells, each one carrying copies of the DNA molecules from the original cell

1.3.2 RNA Sugar: ribose / not 2’-deoxyribose Uracil (U): not thymine (T) not form a double helix

RNA-DNA hybrid helices parts of an RNA molecule may bind to other parts of the

same molecule by complementarity the 3-dimensional structure of RNA is far more varied

than that of DNA function

DNA: perform one function--encoding information RNA: perform different functions: there are different kinds

of RNAs

RNA structureThe three-dimensional structure of RNA is far more varied than that of DNA.

tRNA 2D representation (typical tRNA clover-leaf)

1.4 the mechanisms of molecular genetics DNA: “the blueprint of life”

- information necessary to build each protein or RNA found in an organism is encoded in DNA molecules

outline (1) describe the encoding (2) protein synthesis: how a protein is built out of

DNA (3) how information (or genetic information) in DNA

is passed along from a parent to its offspring.

1.4.1 genes and the genetic code Chromosome and gene

Chromosome– very long DNA molecule• Each cell of an organism has a few chromosomes

gene• Definition: a contiguous stretch of DNA that contains the

information necessary to build a protein or an RNA molecule

• Lengths vary / 10,000 bp for humans• Certain cell mechanisms: capable of recognizing in the

DNA the precise points at which a gene starts and at which it ends

codon and genetic code codon

• Definition: each nucleotide triplet• Role: a gene uses it to “specify” each AA in DNA

1.4.1 genes and the genetic code genetic code

• Definition: the table that gives the correspondence between possible triplet and each AA

• Cause of using RNA bases: RNA molecules provide the link between DNA and actual protein synthesis

1. 64 possible nucleotide triplets correspond to only 20 AAs

2. STOP: 3 codons

3. Exception

Genetic code

1.4.2 Transcription, translation, and protein synthesis

Transcription—process: messager RNA is produced Promoter（启动子） : a region before each gene

in DNA; to serve as an indication to cellular mechanism that a gene is ahead

mRNA: a copy of gene; with exactly the same sequence as one of the strands of the gene but substituting U for T

Introns (内含子 ): parts of a gene / not used in protein synthesis; spliced out from mRNA->shortened mRNA leaves nucleus with exons (外显子 ) plus regulatory region

1.4.2 Transcription, translation, and protein synthesis

1.4.2 Transcription, translation, and protein synthesis

Translation: a process in which mRNA is translated into Protein

tRNA:• Connect between a codon and specific AA• Number of tRNA: varies among species / not 64• Some codens are not represented; some tRNA can

bind to more than one codon

The structure of tRNA

Three bases of tRNA

To bind amino acids

1.4.2 Transcription, translation, and protein synthesis

process• As mRNA passes, tRNA bind to its codon• Its attached AA falls in place just next to previous

AA in protein chain being formed• Enzyme catalyzes AA to protein chain, releasing

it from tRNA• Synthesis ends: when STOP codon appears, no

tRNA with it

See movie

Protein synthesis

1.4.2 Transcription, translation, and protein synthesis

The Central Dogma of Molecular

Biology

DNA RNA Proteintranscript translation

replication

genotype phenotypeException – retroviruses