50
A. Jayaraman et al.
on the melting curves. But as the ε
PP increases from ε
PP
= 1ε to ε
PP
= 5ε, the
melting curves of ONAs conjugated with polymers are shifted to lower temperatures
as compared to unconjugated ONAs for both 40-mer and 100-mer; this is opposite to
the trends seen for neutral and flexible ONAs. In negatively charged and semi-flexible
ONAs, the long-range inter-ONA electrostatic repulsion dominates the short-range
polymer–polymer attraction (solvophobicity), restricting the aggregates to be small
and formed by a few ONA-polymer conjugates. In these small aggregates, the ONA
strands need to adopt a bent conformation to maintain a hybridized duplex, thus,
the ONA duplexes melt at a lower temperature than unconjugated ONA to keep the
small polymer aggregates intact and reduce the entropic penalty associated with the
bent conformations. A representative snapshot of single ONA duplex on top of small
polymer aggregate is shown in the inset of Fig. 5d.
2.5 Limitations and Potential Future Directions
The key results presented above and additional results described in detail in Refs.
[19, 20, 66, 67] all show that our ONA CG model can successfully predict the trends
in melting thermodynamics for ONAs with physical properties such as backbone
flexibility, nucleobase spacing and backbone electrostatics that are different from
DNA. There are few limitations which could be addressed in future studies: At
present, our CG model recognizes only four nucleobases: adenine (A), thymine (T),
cytosine (C) and guanine (G). In future, one may wish to incorporate other types of
nucleobases such as uracil (U). The above thermodynamics focused studies use an
implicit solvent model but future efforts spent toward incorporating explicit solvent
model along with corrected masses of all CG beads would allow one to predict the
kinetics of hybridization/melting phenomena for varying ONA design parameters.
3 Collagen-like Peptides
3.1 Background
Collagen is the most abundant protein in the human body and makes up about onethird of the body’s total protein content [82, 83]. Collagen is an extracellular matrix
(ECM) protein and is important for the structural integrity of many tissues. Moreover,
the mechanical strength and function of collagen have been attributed to its triple
helical structure. Several studies have focused on short collagen mimics, or collagenlike peptides, in order to elucidate the molecular structure and thermal stability of
collagen [82–86]. These collagen-like peptides (CLP) are biopolymers that are made
up of repeat units of (X–Y-G) m amino acid triplets, where X and Y are usually proline
and hydroxyproline, and m is the number of repeat units. Like native collagen, each
A. Jayaraman et al.
on the melting curves. But as the ε
PP increases from ε
PP
= 1ε to ε
PP
= 5ε, the
melting curves of ONAs conjugated with polymers are shifted to lower temperatures
as compared to unconjugated ONAs for both 40-mer and 100-mer; this is opposite to
the trends seen for neutral and flexible ONAs. In negatively charged and semi-flexible
ONAs, the long-range inter-ONA electrostatic repulsion dominates the short-range
polymer–polymer attraction (solvophobicity), restricting the aggregates to be small
and formed by a few ONA-polymer conjugates. In these small aggregates, the ONA
strands need to adopt a bent conformation to maintain a hybridized duplex, thus,
the ONA duplexes melt at a lower temperature than unconjugated ONA to keep the
small polymer aggregates intact and reduce the entropic penalty associated with the
bent conformations. A representative snapshot of single ONA duplex on top of small
polymer aggregate is shown in the inset of Fig. 5d.
2.5 Limitations and Potential Future Directions
The key results presented above and additional results described in detail in Refs.
[19, 20, 66, 67] all show that our ONA CG model can successfully predict the trends
in melting thermodynamics for ONAs with physical properties such as backbone
flexibility, nucleobase spacing and backbone electrostatics that are different from
DNA. There are few limitations which could be addressed in future studies: At
present, our CG model recognizes only four nucleobases: adenine (A), thymine (T),
cytosine (C) and guanine (G). In future, one may wish to incorporate other types of
nucleobases such as uracil (U). The above thermodynamics focused studies use an
implicit solvent model but future efforts spent toward incorporating explicit solvent
model along with corrected masses of all CG beads would allow one to predict the
kinetics of hybridization/melting phenomena for varying ONA design parameters.
3 Collagen-like Peptides
3.1 Background
Collagen is the most abundant protein in the human body and makes up about onethird of the body’s total protein content [82, 83]. Collagen is an extracellular matrix
(ECM) protein and is important for the structural integrity of many tissues. Moreover,
the mechanical strength and function of collagen have been attributed to its triple
helical structure. Several studies have focused on short collagen mimics, or collagenlike peptides, in order to elucidate the molecular structure and thermal stability of
collagen [82–86]. These collagen-like peptides (CLP) are biopolymers that are made
up of repeat units of (X–Y-G) m amino acid triplets, where X and Y are usually proline
and hydroxyproline, and m is the number of repeat units. Like native collagen, each